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Chronic pressure overload (PO) is associated with cardiac hypertrophy and altered autonomic control of cardiac function, in which the latter may involve adaptations in central and/or peripheral cardiac neural control mechanisms. To evaluate the specific remodeling of the intrinsic cardiac nervous system following pressure overload, the descending thoracic aorta artery of the guinea pig was constricted ~20%, and the animals recovered for 9 wk. Thereafter, atrial neurons of the intrinsic cardiac plexus were isolated for electrophysiological and immunohistochemical analyses. Intracellular voltage recordings from intrinsic cardiac neurons demonstrated no significant changes in passive membrane properties or action potential depolarization compared with age-matched controls and sham-operated animals, but afterhyperpolarization duration was increased in PO animals. Neuronal excitability, as determined by the number of action potentials produced with depolarizing stimuli, was differentially increased in phasic neurons derived from PO animals in response to exogenously applied histamine compared with sham and age-matched controls. Conversely, pituitary adenylate cyclase-activating polypeptide-induced increases in intrinsic cardiac neuron evoked AP frequency were similar between control and PO animals. Immunohistochemical analysis demonstrated a twofold increase in the percentage of neurons immunoreactive for neuronal nitric oxide synthase in PO animals compared with control. The density of mast cells within the intrinsic cardiac plexus from PO animals was also increased twofold compared with preparations from control animals. These results indicate that congestive heart failure associated with chronic pressure overload induces a differential remodeling of intrinsic cardiac neurons and upregulation of neuronal responsiveness to specific neuromodulators. intrinsic cardiac nervous system; histamine; pituitary adenylate cyclase-activating polypeptide; mast cells; nitric oxide synthase; intracellular recording

We investigated the effect of inflammation on slow synaptic transmission in myenteric neurons in the guinea pig ileum. Inflammation was induced by the intraluminal injection of trinitrobenzene sulfonate, and tissues were taken for in vitro investigation 6-7 days later. Brief tetanic stimulation of synaptic inputs (20 Hz, 1 s) induced slow excitatory postsynaptic potentials (EPSPs) in 49% and maintained postsynaptic excitation that lasted from 27 min to 3 h in 13% of neurons from the inflamed ileum. These neurons were classified electrophysiologically as AH neurons; 10 were morphological type II neurons, and one was type I. Such long-term hyperexcitability after a brief stimulus is not encountered in enteric neurons of normal intestine. Electrophysiological properties of neurons with maintained postsynaptic excitation were similar to those of neurons with slow EPSPs. Another form of prolonged excitation, sustained slow postsynaptic excitation (SSPE), induced by 1-Hz, 4-min stimulation, in type II neurons from the inflamed ileum reached its peak earlier but had lower amplitude than that in control. Unlike slow EPSPs and similar to SSPEs, maintained excitation was not inhibited by neurokinin-1 or neurokinin-3 receptor antagonists. Maintained postsynaptic excitation was not influenced by PKC inhibitors, but the PKA inhibitor, H-89, caused further increase in neuronal excitability. In conclusion, maintained excitation, observed only in neurons from the inflamed ileum, may contribute to the dysmotility, pain, and discomfort associated with intestinal inflammation. enteric nervous system; myenteric neurons

Global poverty and food insecurity continue to remain critical issues, especially in rural areas. Developing and fostering agricultural systems that not only require low to moderate amounts of economic capital and few external inputs but also maintain and enhance the resource base of production are key features of sustainable agricultural development. Sustainable agricultural development, including diversifying smallholder production to include livestock, is a pragmatic approach to address both rural poverty and food insecurity. Livestock play important roles in the lives of humans as converters, recyclers and banks of nutrients. Smallholders raise a diversity of livestock species and often raise multiple species simultaneously. High fecundity, diet flexibility and adaptability to a wide range of housing and management approaches are critical traits of livestock species well suited for producing meat for home consumption and marketing in the context of rural smallholders. Swine (Sus scrofa) and chicken (Gallus domesticus) meet many of these criteria and are well known livestock species. This paper examines the potential for a less common species of livestock, guinea pig (Cavia porcellus) to enhance food security and increase household income of rural smallholders. Although cultural acceptance of guinea pig as a source of nutrition and income is less ubiquitous than that of swine, chicken and other species, the biological, ecological and economic advantages of guinea pig deserve further examination by those working to alleviate global poverty and food insecurity. Key words: animal protein, development, guinea pigs, livestock

The motility of the gut depends on the chemicals contained in the lumen, but the stimuli that modify motility and their relationship to enteric neural pathways are unclear. This study examined local inhibitory reflexes activated by various chemical stimulants applied to the mucosa to characterize effective physiological stimuli and the pathways they excite. Segments of the jejunum were dissected to allow access to the circular muscle on one-half of the preparation while leaving the mucosa intact on the circumferentially adjacent half. Chemicals were transiently applied to the mucosa, and responses were recorded intracellularly in nearby circular muscle cells. The amino acids e-phenylalanine, L-alanine, or L-tryptophan (all 1 mM) evoked inhibitory junction potentials (IJPs; latency 150-300 ms, amplitude 3-8 mV, each n > 6) that were blocked by TTX and partially blocked by antagonists of P2X receptors and/or a combination of antagonists at 5-H[T.sub.3] and 5-H[T.sub.4] receptors. The putative mediators 5-HT (10 [micro]M), ATP (1 mM), and CCK-8 (1-10 [micro]M) elicited IJPs mediated via 5-H[T.sub.3], P2X, and CCK-B receptors, respectively. Responses were only partially reduced by the effective antagonists. IJPs evoked by electrically stimulating the mucosa were unaffected by antagonists that reduced chemically evoked responses. Both chemically and electrically evoked IJPs were resistant to nicotinic, NKI, N[K.sub.3], [alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, N-methyl-D-aspartate, or CGRP receptor blockade. We conclude that mucosal stimulation by amino acids activates local neural pathways whose pharmacology depends on the nature of the stimulus. Transmitters involved at some synapses in these pathways remain to be identified. 5-HT3 receptors; P2X receptors; cholecystokinin receptors; enteric reflexes doi:10.1152/ajpgi.00580.2006

Mechanisms underlying nutrient-induced segmentation within the gut are not well understood. We have shown that decanoic acid and some amino acids induce neurally dependent segmentation in guinea pig small intestine in vitro. This study examined the neural mechanisms underlying segmentation in the circular muscle and whether the timing of segmentation contractions also depends on slow waves. Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and jejunum. Video imaging was used to monitor intestinal diameter as a function of both longitudinal position and time. Circular muscle electrical activity was recorded by using suction electrodes. Recordings from sites of segmenting contractions showed they are always associated with excitatory junction potentials leading to action potentials. Recordings from sites oral and anal to segmenting contractions revealed inhibitory junction potentials that were time locked to those contractions. Slow waves were never observed underlying segmenting contractions. In paralyzed preparations, intracellular recording revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast, the frequencies of segmenting contractions varied widely (duodenum: 3.6-28.8 c/min, median 10.8 c/min; jejunum: 3.0-27.0 c/min, median 7.8 c/min) and sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced segmentation contractions in guinea pig small intestine do not depend on slow-wave activity. Rather they result from a neural circuit producing rhythmic localized activity in excitatory motor neurons, while simultaneously activating surrounding inhibitory motor neurons. enteric nervous system; intestinal motility patterns; slow waves

We are developing two types of vestibular prosthetics that electrically stimulate afferent neurons. One type replaces absent sensory function by providing stimulation that modulates above and below a baseline established with the head stationary. The other type provides constant stimulation and is turned on only when necessary, for example, to override unnatural variations like those experienced by patients suffering from Meniere's syndrome; this prosthesis does not provide motion information. Both prostheses require neural plasticity, which we investigated by providing chronic constant-rate stimulation to semicircular canal neurons in three guinea pigs. The stimulation was alternately switched on or off for eight consecutive weeks before being switched daily. A brisk horizontal nystagmus was measured when the stimulation was first turned on and then dissipated over the course of a day. The nystagmus demonstrated an after-effect in the opposite direction when the stimulation was turned off. The nystagmus that we measured after just a few (2 to 5) off-to-on transitions returned to baseline more rapidly than when first turned on. In fact, after many such off-to-on or on-to-off transitions, little nystagmus was evoked by turning the stimulation on or off. These findings show that the brain acclimates to constant-rate stimulation. Index Terms--Adaptation, guinea pig, neural prosthesis, vestibular implant, vestibulo-ocular reflex, VOR.

Experiments carried out in conscious guinea pigs suggest that citric acid-0evoked coughing is partly mediated by transient receptor potential vanilloid type 1 (TRPV1) receptor-dependent activation of tachykinin-containing, capsaicin-sensitive C fibers. In vitro electrophysiological analyses indicate, however, that acid also activates capsaicin-sensitive and -insensitive vagal afferent nerves by a TRPV1-independent mechanism, and studies in anesthetized guinea pigs show that coughing evoked by acid is mediated by activation of capsaicin-insensitive vagal afferent nerves. In the present study, we have characterized the mechanisms of citric acid-evoked coughing in anesthetized guinea pigs. Drugs were administered directly to the Krebs buffer perfusing the extrathoracic trachea. Citric acid was applied topically to the tracheal mucosa, directly into the tracheal perfusate in increasing concentrations and at 1-min intervals. Citric acid dose dependently evoked coughing in anesthetized guinea pigs. This was mimicked by hydrochloric acid but not by sodium citrate. The coughing evoked by acid was nearly or completely abolished by TTX or by cutting the recurrent laryngeal nerves. Perfusing the trachea with a low [Cl.sup.-] buffer potentiated the acid-induced cough reflex. In contrast, prior capsaicin desensitization, 10 [micro]M capsazepine, [Ca.sup.2+]-free perfusate, 0.1 [micro]M iberiotoxin, 1 [micro]M atropine, 10 [micro]M isoproterenol, 10 [micro]M albuterol, 3 [micro]M indomethacin, 0.1 [micro]M HOE-140, a combination of [neurokinin.sub.1] (N[K.sub.1]; CP-99994), N[K.sub.2] (SR-48968), and N[K.sub.3] (SB-223412) receptor antagonists (0.1 p[micro]M each), a combination of histamine [H.sub.1] (3 [micro]M pyrilamine) and cysL[T.sub.1] (1 [micro]M ICI-198615) receptor antagonists, superior laryngeal nerve transection, or epithelium removal did not inhibit citric acid-evoked coughing. These and other data indicate that citric acid-evoked coughing in anesthetized guinea pigs is mediated by direct activation of capsaicin-insensitive vagal afferent nerves, perhaps through sequential activation of acid-sensing ion channels and chloride channels. TRPV1; capsaicin; rapidly adapting receptor doi:10.1152/ajpregu.00862.2005

The transient outward current ([I.sub.to]) is a major repolarizing current in the heart. Marked reduction of Ito density occurs in heart failure and is accompanied by significant action potential duration (APD) prolongation. To understand the species-dependent role of [I.sub.to] in regulating the ventricular action potential morphology and duration, we introduced simulated [I.sub.to] conductance in guinea pig and canine endocardial ventricular myocytes using the dynamic clamp technique and perforated patch-clamp recordings. The effects of simulated [I.sub.to] in both types of cells were complex and biphasic, separated by a clear density threshold of ~40 pA/pF. Below this threshold, simulated [I.sub.to] resulted in a distinct phase 1 notch and had little effect on or moderately prolonged the APD. [I.sub.to] above the threshold resulted in all-or-none repolarization and precipitously reduced the APD. Qualitatively, these results agreed with our previous studies in canine ventricular cells using whole cell recordings. We conclude that 1) contrary to previous gene transfer studies involving the Kv4.3 current, the response of guinea pig ventricular myocytes to a fully inactivating [I.sub.to] is similar to that of canine ventricular cells and 2) in animals such as dogs that have a broad cardiac action potential, [I.sub.to] does not play a major role in setting the APD. dynamic clamp; transient outward current; ventricular myocytes doi:10.1152/ajpheart.00084.2006

The severity of epidemic and pandemic influenza outbreaks is dictated in part by the efficiency with which the causative strain transmits between human hosts. The mechanisms underlying influenza virus spread are poorly understood, in part because of the lack of a convenient animal model to study this phenomenon. Indeed, despite extremely efficient transmission among humans and virulence in the mouse model, we have shown that even the 1918 pandemic influenza virus does not transmit between mice. We therefore evaluated the guinea pig as a model mammalian host for influenza virus. Using the recent human isolate A/Panama/ 2007/99 (Pan/99) (H3N2) virus, we found that guinea pigs were highly susceptible to infection with the unadapted virus ([ID.sub.50] = 5 plaque-forming units). Pan/99 virus grew to high titers in the upper respiratory tract and was shed in nasal washings of infected animals. Moreover, influenza virus was transmitted from infected guinea pigs to noninfected guinea pigs housed in the same cage, an adjacent cage, and a cage placed 91 cm away. Our results demonstrate that influenza virus can pass between guinea pigs by means of droplet spread and thereby establish the suitability of the guinea pig as a model host for influenza virus transmission studies. avian influenza virus | contact spread | droplet spread | pandemic | sentinel

Because the onset of fever induced by intravenously (iv) injected bacterial endotoxic lipopolysaccharides (LPS) precedes the appearance in the bloodstream of pyrogenic cytokines, the presumptive peripheral triggers of the febrile response, we have postulated previously that, in their stead, PG[E.sub.2] could be the peripheral fever trigger because it appears in blood coincidentally with the initial body core temperature ([T.sub.c]) rise. To test this hypothesis, we injected Salmonella enteritidis LPS (2 [micro]g/kg body wt iv) into conscious guinea pigs and measured their plasma levels of LPS, PG[E.sub.2], TNF-[alpha], IL-1[beta], and IL-6 before and 15, 30, 60, 90, and 120 min after LPS administration; [T.sub.c]. was monitored continuously. The animals were untreated or Kupffer cell (KC) depleted; the essential involvement of KCs in LPS fever was shown previously. LPS very promptly (< 10 min) induced a rise of T,. that was temporally correlated with the elevation of plasma PG[E.sub.2]. KC depletion prevented the [T.sub.c] and plasma PG[E.sub.2] rises and slowed the clearance of LPS from the blood. TNF-[alpha] was not detectable in plasma until 30 min and in IL-1[beta] and IL-6 until 60 min after LPS injection. KC depletion did not alter the times of appearance or magnitudes of rises of these cytokines, except TNF-[alpha], the maximal level of which was increased approximately twofold in the KC-depleted animals. In a follow-up experiment, PG[E.sub.2] antiserum administered iv 10 min before LPS significantly attenuated the febrile response to LPS. Together, these results support the view that, in guinea pigs, PG[E.sub.2] rather than pyrogenic cytokines is generated by KCs in immediate response to iv LPS and triggers the febrile response. fever; tumor necrosis factor-[alpha]; interleukin-l[beta]; interleukin-6; liver; complement

The authors compared interactions of infants with mothers and unfamiliar females in a novel environment in 2 caviomorph rodent species: the harem-living Cavia aperea, the probable progenitor of the domestic guinea pig; and the pair-living Galea monasteriensis. In C. aperea, interactions with mothers and unfamiliar females were largely similar; in G. monasteriensis, interactions with the mother, but not unfamiliar female, were characterized by physical closeness and sociopositive behavior. In G. monasteriensis, plasma cortisol levels were lower when with the mother than when with the unfamiliar female. Results are consistent with the species' social organizations and suggest that behavioral interactions of pups with mothers and other females in domestic guinea pigs reflect primarily the social organization of the progenitor species rather than domestication. Keywords: infant-adult interaction, filial attachment, social organization, caviomorph rodent, guinea pig

Histamine, released from mast cells, can modulate the activity of intrinsic neurons in the guinea pig cardiac plexus. The present study examined the ionic mechanisms underlying the histamine-induced responses in these cells. Histamine evokes a small membrane depolarization and an increase in neuronal excitability. Using intracellular voltage recording from individual intracardiac neurons, we were able to demonstrate that removal of extracellular sodium reduced the membrane depolarization, whereas inhibition of [K.sup.+] channels by 1 mM [Ba.sup.2+], 2 mM [Cs.sup.+], or 5 mM tetraethylammonium had no effect. The depolarization was also not inhibited by either 10 [micro]M [Gd.sup.3+] or a reduced [Cl.sup.-] solution. The histamine-induced increase in excitability was unaffected by [K.sup.+] channel inhibitors; however, it was reduced by either blockage of voltage-gated [Ca.sup.2+] channels with 200 [micro]M [Cd.sup.2+] or replacement of extracellular [Ca.sup.2+] with [Mg.sup.2+]. Conversely, alterations in intracellular calcium with thapsigargin or caffeine did not inhibit the histamine-induced effects. However, in cells treated with both thapsigargin and caffeine to deplete internal calcium stores, the histamine-induced increase in excitability was decreased. Treatment with the phospholipase C inhibitor U73122 also prevented both the depolarization and the increase in excitability. From these data, we conclude that histamine, via activation of [H.sub.1] receptors, activates phospholipase C, which results in 1) the opening of a nonspecific cation channel, such as a transient receptor potential channel 4 or 5; and 2) in combination with either the influx of [Ca.sup.2+] through voltage-gated channels or the release of internal calcium stores leads to an increase in excitability. tetraethylammonium; phospholipase C; mast cells; [H.sub.1] receptor

Previously, we showed the shortening velocity of guinea pig tracheal strips was the greatest in juvenile (3-wk-old) compared with infant (1-wk-old) and adult animals (3-mo-old). The greatest shortening velocity was associated with the least resistance to shortening calculated from force-velocity curves among the three age groups. It remained to be verified if the stiffness of tracheal tissue, a measure of tissue response to geometrical deformations, is different among the three age groups. We hypothesized that stiffness of intact tracheal strips is lowest in the juvenile group and that this can explain the ontogeny of airway smooth muscle resistance to shortening and shortening velocity. Static stiffness measured through stepwise deformations showed no age-related differences. Evaluation of tissue response to oscillatory deformations showed that the dynamic stiffness of unstimulated tracheal strips was 8.35 [+ or -] 0.88, 4.15 [+ or -] 1.09, and 8.21 [+ or -] 1.57 kPa, and the phase angle was 10.3 [+ or -] 2.93, 2.46 [+ or -] 0.67, and 7.87 [+ or -] 1.77[degrees] in infant, juvenile, and adult, respectively. Unstimulated juvenile strips were significantly lower in dynamic stiffness and phase angle compared with unstimulated infant or adult strips. This maturational profile was independent of muscle strip preset length or oscillation mode/amplitude but was abolished at peak of contraction to either carbachol or electric field stimulation. These results suggest that the noncontractile components of tracheal strips are less stiff and contain fewer viscous/frictional elements in juvenile than in other age groups. This may provide a functional basis for reduced resistance to length changes in juvenile airway smooth muscle. ontogenesis; viscoelasticity

The aim was to determine the role CGRP and/or tachykinins released from sensory neural mechanisms in enteric neural vasodilator pathways. These pathways project through the myenteric plexus to submucosal vasodilator neurons. Submucosal arterioles were exposed in the distal portion of an in vitro combined submucosal-myenteric guinea pig ileal preparation, and dilation was monitored with videomicroscopy. Vasodilator neural reflexes were activated by gently stroking the mucosa with a fine brush or by distending a balloon placed beneath the flat-sheet preparation in the proximal portion. Dilations evoked by mucosal stroking were inhibited 64% by the CGRP 8-37 and 37% by N[K.sub.3] (SR 142801) antagonists. When the two antagonists were combined with hexamethonium, only a small vasodilation persisted. Balloon distension-evoked vasodilations were inhibited by N[K.sub.3] antagonists (66%) but were not altered by CGRP 8-37. In preparations in which myenteric descending interneurons were directly activated by electrical stimulation, combined application of CGRP 8-37 and the NK antagonists had no effect. Stimulation of capsaicin sensitive nerves in the myenteric plexus did not activate these vasodilator reflexes. These findings suggest that mucosal-activated reflexes result from the release of CGRP and tachykinins from enteric sensory neurons. Distension-evoked responses were significantly blocked by N[K.sub.3] antagonists, suggesting that stretch activation of myenteric sensory neurons release tachykinins that activate N[K.sub.3] receptors on myenteric vasodilator pathways. intrinsic primary afferent neuron; vasodilation; submucosal plexus; submucosal arterioles; tachykinins; calcitonin gene-related peptide

We reported previously that the onset of LPS-induced fever, irrespective of its route of administration, is temporally correlated with the appearance of LPS in the liver and that splenectomy significantly increases both the febrile response to LPS and the uptake of LPS by Kupffer cells (KC). To further evaluate the role of the spleen in LPS fever production, we ligated the splenic vein and, 7 and 30 days later, monitored the core temperature changes over 6 h after intraperitoneal (ip) injection of LPS (2 [micro]g/kg). Both the febrile response and the uptake of LPS by KC were significantly augmented. Like splenectomy, splenic vein ligation (SVL) increased the febrile response and LPS uptake by KC until the collateral circulation developed, suggesting that the spleen may normally contribute an inhibitory factor that limits KC uptake of LPS and thus affects the febrile response. Subsequently, to verify the presence of this factor, we prepared splenic extracts from guinea pigs pretreated with LPS (8 [micro]g/kg ip) or pyrogen-free saline, homogenized and ultrafiltered them, and injected them intravenously into splenectomized (Splex) guinea pigs pretreated with LPS (8 [micro]g/kg ip). The results confirmed our presumption that the splenic extract from LPS-treated guinea pigs inhibits the exaggerated febrile response and the LPS uptake by the liver of Splex guinea pigs, indicating the presence of a putative splenic inhibitory factor, confirming the participation of the spleen in LPS-induced fever, and suggesting the existence of a novel antihyperpyretic mechanism. Preliminary data indicate that this factor is a lipid. Kupffer cells; fluorescein isothiocyanate-labeled lipopolysaccharide; antipyresis; splenic vein ligation

The guinea pig rectum, but not the colon, is innervated by a specialized class of distension-sensitive mechanoreceptors that have transduction sites corresponding to rectal intraganglionic laminar endings (rIGLEs). Rectal mechanoreceptors recorded in vitro had low threshold to circumferential stretch, adapted slowly, and could respond within 2 ms to mechanical stimulation by a piezo-electric probe. Antagonists to ionotropic N-methyl-D-aspartate (NMDA; CGS 19755, memantine) and non-NMDA (6,7-dinitroquinoxaline-2,3-dione) glutamate receptors did not affect mechanotransduction. In normal Krebs solution, the P2X purinoreceptor agonist [alpha],[beta]-methylene ATP reduced mechanoreceptor firing evoked by distension but simultaneously relaxed circular smooth muscle and inhibited stretch-induced contractions. Neither ATP nor [alpha],[beta]-methylene ATP affected mechanotransduction when transduction sites were directly compressed with von Frey hairs. The P2 purinoreceptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid did not affect stretch-induced firing but reduced the inhibitory effect of [alpha],[beta]-methylene ATP on stretch-induced firing. Under isometric conditions, blocking synaptic transmission in [Ca.sup.2+]-free solution reduced stretch-evoked firing but not when basal tension was restored to control levels. Under isotonic condition, [Ca.sup.2+]-free solution did not significantly affect load-evoked firing. The blockers of mechanogated and/or transient receptor potential channels, benzamil, [Gd.sup.3+], SKF 96365, and ruthenium red inhibited stretch-induced firing but, in parallel, significantly reduced stretch-induced contractions. Benzamil and SKF 96365 were able to inhibit mechanotransduction when transduction sites were compressed with von Frey hairs. The results show that mechanotransduction is rapid but does not depend on fast exocytotic release of mediators. It is likely that stretch-activated ion channels on rIGLEs are involved in direct, physical mechanotransduction by rectal low-threshold mechanoreceptors. afferents; mechanosensory transduction

Small mammals usually produce large litters of altricial young, resulting in high reproductive rates. In contrast, cavies give birth to few precocial young after a long gestation. The price of this reproductive strategy is a low intrinsic rate of natural increase. We investigated if the patterns of reproduction in a wild population of Cavia magna are consistent with the hypotheses that cavies can increase their reproductive output by breeding aseasonally and by maturing extremely early. We collected data on reproduction and growth by capture--recapture during a 26-month field study in a wetland in Uruguay, and from a laboratory population founded with individuals from the same region. Among the Caviinae, C. magna is particularly precocial, with individual neonates weighing on average 18% of maternal mass. Reproduction was mostly seasonal, with the main birth season starting at the end of September (austral spring) and extending until May in 1999 and February in 2000, respectively, with only a few females reproducing during the 1st but not the 2nd austral winter. Individual females produced on average 3 litters per year. Some females born in early spring conceived successfully between the age of 30 and 45 days, similar to females in the laboratory. The remainder of the 1st spring cohort and females of subsequent birth cohorts delayed reproduction until the following spring. Body condition and growth rates were highest in the spring, declined through the year, and varied between years, and may be the proximate factors determining whether an adult female or a juvenile initiates breeding. Breeding opportunistically whenever conditions allow might partly compensate for the low reproductive rate of cavies. Key words: age at maturity, Cavia magna, cavies, growth rates, life history, opportunistic breeding, precocial small mammals, reproductive strategy

In guinea pigs, dose-dependent febrile responses were induced by injection of a high (100 [micro]g/kg) or a low (10 [micro]g/kg) dose of bacterial lipopolysaccharide (LPS) into artificial subcutaneously implanted Teflon chambers. Both LPS doses further induced a pronounced formation of prostaglandin [E.sub.2] (PG[E.sub.2]) at the site of localized subcutaneous inflammation. Administration of diclofenac, a nonselective cyclooxygenase (COX) inhibitor, at different doses (5, 50, 500, or 5,000 [micro]g/kg) attenuated or abrogated LPS-induced fever and inhibited LPS-induced local PG[E.sub.2] formation (5 or 500 [micro]g/kg diclofenac). Even the lowest dose of diclofenac (5 [micro]g/kg) attenuated fever in response to 10 [micro]g/kg LPS, but only when administered directly into the subcutaneous chamber, and not into the site contralateral to the chamber. This observation indicated that a localized formation of PG[E.sub.2] at the site of inflammation mediated a portion of the febrile response, which was induced by injection of 10 [micro]g/kg LPS into the subcutaneous chamber. Further support for this hypothesis derived from the observation that we failed to detect elevated amounts of COX-2 mRNA in the brain of guinea pigs injected subcutaneously with 10 [micro]g/kg LPS, whereas subcutaneous injections of 100 [micro]g/kg LPS, as well as systemic injections of LPS (intra-arterial or intraperitoneal routes), readily caused expression of the COX-2 gene in the guinea pig brain, as demonstrated by in situ hybridization. Therefore, fever in response to subcutaneous injection of 10 [micro]g/kg LPS may, in part, have been evoked by a neural, rather than a humoral, pathway from the local site of inflammation to the brain. lipopolysaccharide; febrile response; prostaglandin [E.sub.2]; cyclooxygenase-2; immune system-to-brain communication

Ischemic preconditioning (IPC) induces distinctive changes in mitochondrial bioenergetics during warm (37[degrees]C) ischemia and improves function and tissue viability on reperfusion. We examined whether IPC before 2 h of hypothermic (27[degrees]C) ischemia affords additive cardioprotection and improves mitochondrial redox balance assessed by mitochondrial NADH and ftavin adenine dinucleotide (FAD) autofluorescence in intact hearts. A mediating role of ATP-sensitive [K.sup.+] ([K.sub.ATP]) channel opening was investigated. NADH and FAD fluorescence was measured in the left ventricular wall of guinea pig isolated hearts assigned to five groups of eight animals each: hypothermia alone, hypothermia with ischemia, IPC with cold ischemia, 5-hydroxydecanoic acid (5-HD) alone, and 5-HD with IPC and cold ischemia. IPC consisted of two 5-min periods of warm global ischemia spaced 5 min apart and 15 min of reperfusion before 2 h of ischemia at 27[degrees]C and 2 h of warm reperfusion. The [K.sub.ATP] channel inhibitor 5-HD was perfused from 5 min before until 5 min after IPC. IPC before 2 h of ischemia at 27[degrees]C led to better recovery of function and less tissue damage on reperfusion than did 27[degrees]C ischemia alone. These improvements were preceded by attenuated increases in NADH and decreases in FAD during cold ischemia and the reverse changes during warm reperfusion. 5-HD blocked each of these changes induced by IPC. This study indicates that IPC induces additive cardioprotection with mild hypothermic ischemia by improving mitochondrial bioenergetics during and after ischemia. Because effects of IPC on subsequent changes in NADH and FAD were inhibited by 5-HD, this suggests that mitochondrial [K.sub.ATP] channel opening plays a substantial role in improving mitochondrial bioenergetics throughout mild hypothermic ischemia and reperfusion. nicotinamide adenine dinucleotide; flavin adenine dinucleotide; ATP-sensitive potassium channels; 5-hydroxydecanoic acid

Ethanol strongly augments secretin-stimulated, but not acetylcholine (ACh)-stimulated, fluid secretion from pancreatic duct cells. To understand its mechanism of action, we examined the effect of short-chain n-alcohols on fluid secretion and intracellular [Ca.sup.2+] concentration ([[Ca.sup.2+].sub.i]) in guinea pig pancreatic ducts. Fluid secretion was measured by monitoring the luminal volume of isolated interlobular ducts. [[Ca.sup.2+].sub.i] was estimated using fura-2 microfluorometry. Methanol and ethanol at 0.3-10 mM concentrations significantly augmented fluid secretion and induced a transient elevation of [[Ca.sup.2+].sub.i] in secretin- or dibulyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-stimulated ducts. However, they failed to affect fluid secretion and [[Ca.sup.2+].sub.i] in unstimulated and ACh-stimulated ducts. In contrast, propanol and butanol at 0.3-10 mM concentrations significantly reduced fluid secretion and decreased [[Ca.sup.2+].sub.i] in unstimulated ducts and in ducts stimulated with secretin, DBcAMP, or ACh. Both stimulatory and inhibitory effects of n-alcohols completely disappeared after their removal from the perfusate. Propanol and butanol inhibited the plateau phase, but not the initial peak, of [[Ca.sup.2+].sub.i], response to ACh as well as the [[Ca.sup.2+].sub.i] elevation induced by thapsigargin, suggesting that they inhibit [Ca.sup.2+] influx. Removal of extracellular [Ca.sup.2+] reduced [[Ca.sup.2+].sub.i] in duct cells and completely abolished secretin-stimulated fluid secretion. In conclusion, there is a distinct cutoff point between ethanol (C2) and propanol (C3) in their effects on fluid secretion and [[Ca.sup.2+].sub.i] in duct cells. Short-chain n-alcohols appear to affect pancreatic ductal fluid secretion by activating or inhibiting the plasma membrane [Ca.sup.2+] channel. intracellular calcium; acetylcholine

Stimulation of [beta]-adrenoceptors contributes to the relaxation of urinary bladder smooth muscle (UBSM) through activation of large-conductance [Ca.sup.2+]-activated [K.sup.+] (BK) channels. We examined the mechanisms by which [beta]-adrenoceptor stimulation leads to an elevation of the activity of BK channels in UBSM. Depolarization from -70 to +10 mV evokes an inward L-type dihydropyridine-sensitive voltage-dependent [Ca.sup.2+] channel (VDCC) current, followed by outward steady-state and transient BK current. In the presence of ryanodine, which blocks the transient BK currents, isoproterenol, a nonselective [beta]-adrenoceptor agonist, increased the VDCC current by ~25% and the steady-state BK current by ~30%. In the presence of the BK channel inhibitor iberiotoxin, isoproterenol did not cause activation of the remaining steady-state [K.sup.+] current component. Decreasing [Ca.sup.2+] influx through VDCC by nifedipine or depolarization to +80 mV suppressed the isoproterenol-induced activation of the steady-state BK current. Unlike forskolin, isoproterenol did not change significantly the open probability of single BK channels in the absence of [Ca.sup.2+] sparks and with VDCC inhibited by nifedipine. Isoproterenol elevated [Ca.sup.2+] spark (local intracellular [Ca.sup.2+] release through ryanodine receptors of the sarcoplasmic reticulum) frequency and associated transient BK currents by ~1.4-fold. The data support the concept that in UBSM [beta]-adrenoceptor stimulation activates BK channels by elevating [Ca.sup.2+] influx through VDCC and by increasing [Ca.sup.2+] sparks, but not through a [Ca.sup.2+]-independent mechanism. This study reveals key regulatory molecular and cellular mechanisms of [beta]-adrenergic regulation of BK channels in UBSM that could provide new targets liar drugs in the treatment of bladder dysfunction. [Ca.sup.2+] sparks; voltage-dependent [Ca.sup.2+] channel; ryanodine receptor

Ruge, Toralph, Lucyna Neuger, Valentina Sukonina, Gengshu Wu, Stefan Barath, Jitendra Gupta, Barbara Frankel, Bjorn Christophersen, Knut Nordstoga, Thomas Olivecrona, and Gunilla Olivecrona. Lipoprotein lipase in the kidney: activity varies widely among animal species. Am J Physiol Renal Physiol 287: F113l-F1139, 2004. First published August 3, 2004; doi: 10.1152/ ajprenal.00089.2004.--Much evidence points to a relationship among kidney disease, lipoprotein metabolism, and the enzyme lipoprotein lipase (LPL), but there is little information on LPL in the kidney. The range of LPL activity in the kidney in five species differed by >500-fold. The highest activity was in mink, followed by mice, Chinese hamsters, and rats, whereas the activity was low in guinea pigs. In contrast, the ranges for LPL activities in heart and adipose tissue were less than six- and fourfold, respectively. The activity in the kidney (in mice) decreased by >50% on food deprivation for 6 h without corresponding changes in mRNA or mass. This decrease in LPL activity did not occur when transcription was blocked with actinomycin D. Immunostaining for kidney LPL in mice and mink indicated that the enzyme is produced in tubular epithelial cells. To explore the previously suggested possibility that the negatively charged glomerular filter picks up LPL from the blood, bovine LPL was injected into rats and mice. This resulted in decoration of the glomerular capillary network with LPL. This study shows that in some species LPL is produced in the kidney and is subject to nutritional regulation by a posttranscriptional mechanism. In addition, LPL can be picked up from blood in the glomerulus. rat; mink; Chinese hamster; mouse; guinea pig; immunolocalization; nutritional regulation; transcription

This study aims to elucidate the social system of the wild cavy (Cavia aperea), the feral ancestor of the domestic guinea pig, whose behavior under natural conditions is almost unstudied. Therefore, a population of C. aperea was investigated for a 6-month period in its natural habitat in southeastern Brazil. The animals' space use was examined via radiotelemetry, social interactions were recorded using direct observations, and genetic relationships were analyzed via DNA fingerprinting. Additionally, the distribution of plant cover, food resources, and predation risk was recorded to investigate the impact of different ecological factors on evolution of the social system. In the study period, a low population density was detected and a strong predation pressure existed, which resulted in a high mortality rate of C. aperea. Spatial distribution of wild cavies was strongly associated with areas of dense ground vegetation. Within these areas, small groups consisting of 1 male and 1-2 females occupied stable home ranges that overlapped only slightly with home ranges of adjacent groups. Social interactions were restricted mainly to individuals of the same group, and initial analyses of paternity indicate that the females' offspring were sired by the respective group male. The social system and spatial organization of C. aperea are regarded as adaptations to high predation pressure because in dense vegetation small group size reduces the risk of detection by predators. Moreover, habitat use, social interactions, and paternity point to a single-male system in this low-density population of wild cavies. Key words: Carla aperea, habitat use, predation risk, radiotelemetry, single-male system, social system, spatial organization, wild cavy, wild guinea pig

Leukotriene [B.sub.4] (LT[B.sub.4]) is a potent leukocyte chemoattractant recently implicated in the pathogenesis of atherosclerosis. The aim of this study was to assess the effects of LT[B.sub.4] on isolated aortic preparations. Rings of guinea pig aorta were challenged with LT[B.sub.4] for recording mechanical responses and measurements of mediator release, and LT[B.sub.4] receptor (BL[T.sub.1] expression was assessed by RT-PCR. Single concentrations of LT[B.sub.4] induced concentration-dependent contractions that were inhibited by treatment with antihistamines, indomethacin, or the thromboxane receptor antagonist BAYu3405 as well as by denudation of endothelium. In addition, LT[B.sub.4] increased the release of histamine and thromboxane in the bath. The contractions induced by LT[B.sub.4] were inhibited by either the unselective BLT receptor antagonist ONO-4057 or the selective BL[T.sub.1] receptor antagonist U-75302. Pretreatment with all-trans-retinoic acid enhanced the contractions and the release of histamine induced by LT[B.sub.4], without affecting either the contractions induced by histamine or the histamine release evoked by calcium ionophore A23187. Analysis by RT-PCR indicated the expression of a BL[T.sub.1] receptor in the guinea pig aorta and that BL[T.sub.1] receptor mRNA was upregulated after treatment with retinoic acid. These results suggest that LT[B.sub.4] contracts the guinea pig aorta via an indirect mechanism involving the release of histamine and thromboxane and that this BL[T.sub.1] receptor-mediated response can be upregulated by all-trans-retinoic acid. histamine; retinoic acid; endothelium; thromboxane

We investigated whether the airway constrictive response to stimulation of bronchopulmonary C-fiber afferents is altered during the maturation process. Isometric tension was measured in airway rings isolated from three tracheobronchial locations (intrathoracic trachea and main and hilar bronchi) and compared in mature [M, 407 [+ or -] 10 (SE) g body wt, n = 36] and immature (IM, 161 [+ or -] 5 g body wt, n = 35) guinea pigs. Our results showed no difference in the ACh ([10.sup.-5] M)- or KCI (40 mM)-induced contraction between M and IM groups, regardless of the airway location. In sharp contrast, the concentration-response curves of [10.sup.-8] - [10.sup.-6] M capsaicin were distinctly lower in IM hilar bronchi; for example, response to the same concentration of capsaicin ([10.sup.-6] M) was 89.2 [+ or -] 15.3% of the response to [10.sup.-5] M ACh in IM und 284.7 [+ or -] 43.2% in M animals. Similar, but smaller, differences in the bronchoconstrictive response to capsaicin between IM and M groups were also observed in the trachea and main bronchus. Electrical field stimulation induced airway constriction in all three locations in M and IM groups. However, after administration of [10.sup.-6] M atropine and [10.sup.-6] M propranolol, electrical field stimulation-induced contraction was significantly smaller in the hilar bronchus of IM than M animals, and this difference was not prevented by pretreatment with 5 x [10.sup.-5] M indomethacin. Although radioimmunoassay showed no difference in the tissue content of substance P between M and IM airways, the constrictive responses to exogenous substance P and neurokinin A were markedly greater in M airways at all three locations. In conclusion, the constriction of isolated airways evoked by C-fiber stimulation was significantly weaker in the IM guinea pigs, probably because of a less potent effect of tachykinins on the airway smooth muscle. airway smooth muscle: bronchoconstriction; capsaicin; tachykinins; airway reflex

Heme oxygenase (HO), the heme-degrading enzyme, has shown anti-inflammatory effects in several models of pulmonary diseases. HO is induced in airways during asthma; however, its functional role is unclear. Therefore, we evaluated the role of HO on airway inflammation [evaluated by bronchoalveolar lavage (BAL) cellularity and BAL levels of eotaxin, PG[E.sub.2], and proteins], mucus secretion (evaluated by analysis of MUC5AC gene expression and periodic acid-Schiff staining), oxidative stress (evaluated by quantification of 4-hydroxynonenal adducts and carbonylated protein levels in lung homogenates), and airway responsiveness to histamine in ovalbumin (OVA)-sensitized and multiple aerosol OVA or saline-challenged guinea pigs (6 challenges, once daily, OVA group and control group, respectively). Airway inflammation, mucus secretion, oxidative stress, and responsiveness were significantly increased in the OVA group compared with the control group. HO upregulation by repeated administrations of hemin (50 mg/kg ip) significantly decreased airway responsiveness in control animals and airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These effects were reversed by the concomitant administration of the HO inhibitor tin protoporphyrin-IX (50 [micro]mol/kg ip). Repeated administrations of tin protoporphyrin-IX alone significantly increased airway responsiveness in control animals but did not modify airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These results suggest that upregulation of the HO pathway has a significant protective effect against airway inflammation, mucus hypersecretion, oxidative stress, and hyperresponsiveness in a model of allergic asthma in guinea pigs. allergy; free radicals; carbon monoxide; bilirubin

The cardiac [Na.sup.+/[Ca.sup.2+] exchanger (NCX) contributes to cellular injury during hypoxia, as its altered function is largely responsible for a rise in cytosolic [Ca.sup.2+] concentration ([[Ca.sup.2+].sub.i]). In addition, the NCX in guinea pig ventricular myocytes undergoes profound inhibition during hypoxia and rapid reactivation during reoxygenation. The mechanisms underlying these changes in NCX activity are likely complex due to the participation of multiple inhibitory factors including altered cytosolic [Na.sup.+] concentration, pH, and ATP. Our main hypothesis is that oxidative stress is an essential trigger for rapid NCX reactivation in guinea pig ventricular myocytes and is thus a critical factor in determining the timing and magnitude of [Ca.sup.2+] overload. This hypothesis was evaluated in cardiac myocytes using fluorescent indicators to measure [[Ca.sup.2+].sub.i] and oxidative stress. An NCX antisense oligonucleotide was used to decrease NCX protein expression in some experiments. Our results indicate that NCX activity is profoundly inhibited in hypoxic guinea pig ventricular myocytes but is reactivated within 1-2 min of reoxygenation at a time of rising oxidative stress. We also found that several interventions to decrease oxidative stress including antioxidants and diazoxide prevented NCX reactivation and [Ca.sup.2+] overload during reoxygenation. Furthermore, application of exogenous [H.sub.2][O.sub.2] was sufficient by itself to reactivate the NCX during sustained hypoxia and could reverse the suppression of reoxygenation-mediated NCX reactivation by diazoxide. These data suggest that elevated oxidative stress in reoxygenated guinea pig ventricular myocytes is required for rapid NCX reactivation, and thus reactivation should he viewed as an active process rather than being due to the simple decline of NCX inhibition. sodium-calcium exchanger; antioxidants; diazoxide; heart; hypoxia; ischemia

Preference tests in a novel environment (Experiment 1) and unobtrusive observations in a specialized living environment (Experiment 2) examined the attractiveness of various classes of conspecifics for maturing guinea pigs (Cavia porcellus). It was found that (a) the young continued to remain near the mother well beyond weaning; (b) there was increased time spent with unrelated adult females, but not males, after weaning; (c) male and female offspring behaved similarly; and (d) littermates spent considerable time with each other. These results provide no evidence that guinea pigs approaching sexual maturity begin to associate preferentially with novel animals or potential breeding partners. Choices were largely predictable from earlier findings of the ability of various classes of conspecifics to reduce hypothalamic-pituitary-adrenal activity of the young.

We modeledeled in contractile element kinetics derived from the cyclic relationship between myoplasmic [[Ca.sup.2+]], measured by indo 1 fluorescence, and left ventricular pressure (LVP). We estimated model rate constants of the [[Ca.sup.2+]] affinity for troponin C (TnC) on actin (A) filament (TnCA) and actin and myosin (M) cross-bridge (A*M) cycling in intact guinea pig hearts during baseline 37[degrees]C perfusion and evaluated changes at 1) 20 min 17[degrees]C pressure, 2) 30-rain reperfusion (RP) after 30-rain 37[degrees]C global ischemia during 37[degrees]C RP, and 3) 30-rain RP after 240-rain 17[degrees]C global ischemia during 37[degrees]C RP. At 17[degrees]C perfusion versus 37[degrees]C perfusion, the model predicted: A*M binding was less sensitive; A*M dissociation was slower; [Ca.sup.2+] was less likely to bind to TnCA with A*M present; and [Ca.sup.2+] and TnCA binding was less sensitive in the absence of A-M. Model results were consistent with a cold-induced fall in heart rate from 260 beats/rain (37[degrees]C) to 33 beats/min (17[degrees]C), increased diastolic LVP, and increased phasic [Ca.sup.2+]. On RP after 37[degrees]C ischemia vs. 37[degrees]C perfusion, the model predicted the following: A*M binding was less sensitive; A*M dissociation was slower; and [Ca.sup.2+] was less likely to bind to TnCA in the absence of A*M. Model results were consistent with reduced myofilament responsiveness to [[Ca.sup.2+]] and diastolic contracture on 37[degrees]C RP. In contrast, after cold ischemia versus 37[degrees]C perfusion, A*M association and dissociation rates, and [Ca.sup.2+] and TnCA association rates, returned to preischemic values, whereas the dissociation rate of [Ca.sup.2+] from A*M was ninefold faster. This cardiac muscle kinetic model predicted a better-restored relationship between [Ca.sup.2+] and cross-bridge function on RP after an eightfold longer period of 17[degrees]C than 37[degrees]C ischemia. indo 1; ischemia-reperfusion injury; hypothermia; isolated hearts; four-state model

In vitro antigen challenge has multiple effects on the excitability of guinea pig bronchial parasympathetic ganglion neurons, including depolarization, causing phasic neurons to fire with a repetitive action potential pattern and potentiating synaptic transmission. In the present study, guinea pigs were passively sensitized to the antigen ovalbumin. After sensitization, the bronchi were prepared for in vitro electrophysiological intracellular recording of parasympathetic ganglia neurons to investigate the contribution of cyclooxygenase activation and prostanoids on parasympathetic nerve activity. Cyclooxygenase inhibition with either indomethacin or piroxicam before in vitro antigen challenge blocked the change in accommodation. These cyclooxygenase inhibitors also blocked the release of prostaglandin [D.sub.2] (PG[D.sub.2]) from bronchial tissue during antigen challenge. We also determined that PG[E.sub.2] and PG[D.sub.2] decreased the duration of the action potential after hyperpolarization, whereas PG[F.sub.2.sub.[alpha]] potentiated synaptic transmission. Thus prostaglandins released during antigen challenge have multiple effects on the excitability of guinea pig bronchial parasympathetic ganglia neurons, which may consequently affect the output from these neurons and thereby alter parasympathetic tone in the lower airways. asthma; bronchoconstriction; synaptic transmission; ganglia; guinea pig

Submucosal cholinergic and noncholinergic neurons in intestines have been shown to be involved in regulating epithelial transport functions, particularly stimulating [Cl.sup.-] secretion. This study investigates the role of submucosal cholinergic neurons in regulating electrogenic [Na.sup.+] absorption in distal colon. Amiloride-sensitive short-circuit current ([I.sub.sc]) and [sup.22][Na.sup.+] flux were measured in mucosal and mucosal-submucosal preparations mounted in Ussing chambers. In the mucosal preparation, carbachol (CCh) added to the serosal side inhibited amiloride-sensitive [I.sub.sc] and amiloride-sensitive [sup.22][Na.sup.+] absorption. The inhibitory effect of CCh was observed at ~0.1 [micro]M, and maximum inhibition of ~70% was attained at ~30 [micro]M (I[C.sub.50] = ~1 [micro]M). CCh-induced inhibition of amiloride-sensitive [I.sub.sc] was almost totally abolished by 10 [micro]M atropine. Treatment of the tissue with ionomycin markedly reduced amiloride-sensitive [I.sub.sc], but a subsequent addition of CCh further decreased it. Also, CCh still had an inhibitory effect, although significantly attenuated, after the tissue had been incubated with a low-[Ca.sup.2+] solution containing ionomycin and BAPTA-AM. Applying electrical field stimulation to submucosal neurons in the mucosal-submucosal preparation resulted in inhibition of amiloride-sensitive [I.sub.sc], ~33% of this inhibition being atropine sensitive. Physostigmine inhibited amiloride-sensitive [I.sub.sc], this effect being abolished by atropine. In conclusion, submucosal cholinergic and noncholinergic neurons were involved in inhibiting electrogenic [Na.sup.+] absorption in colon. This inhibition by cholinergic neurons was mediated by muscarinic receptor activation. enteric nerve; intracellular [Ca.sup.2+]; acetylcholine; intestinal secretion; epithelial [Na.sup.+] channel

Cell-attached recordings revealed [Cl.sup.-] channel activity in basolateral membrane of guinea pig distal colonic crypts isolated from basement membrane. Outwardly rectified currents ([sup.gp][Cl.sub.or]) were apparent with a single-channel conductance ([gamma]) of 29 pS at resting membrane electrical potential; another outward rectifier with [gamma] of 24 pS was also observed (~25% of [sup.gp][Cl.sub.or]). At a holding potential of -80 mV [gamma] was 18 pS for both [sup.gp][Cl.sub.or] currents, and at +80 mV [gamma] was 67 and 40 pS, respectively. Identity as [Cl.sup.-] channels was confirmed in excised patches by changing bath ion composition. From reversal potentials, relative permeability of [K.sup.+] over [Cl.sup.-] ([P.sub.K]/[P.sub.Cl]) was 0.07 [+ or -] 0.03, with relative permeability of [Na.sup.+] over [Cl.sup.-] ([P.sub.Na]/[P.sub.Cl]) = 0.08 [+ or -] 0.04. A second type of [Cl.sup.-] channel was seen with linear current-voltage (I-V) relations ([sup.gp][Cl.sub.L]), having subtypes with [gamma] of 21, 13, and 8 pS. Epinephrine or forskolin increased the number of open [sup.gp][Cl.sub.or] and [sup.gp][Cl.sub.L]. Open probabilities ([P.sub.o]) of [sup.gp][Cl.sub.or], [sup.gp][Cl.sub.L21], and [sup.gp][Cl.sub.L13] were voltage dependent in cell-attached patches, higher at more positive potentials. Kinetics of [sup.gp][Cl.sub.or] were more rapid with epinephrine activation than with forskolin activation. Epinephrine increased [P.sub.o] at the resting membrane potential for [sup.gp][Cl.sub.L13]. Secretagogue activation of these [Cl.sup.-] channels may contribute to stimulation of electrogenic [K.sup.+] secretion across colonic epithelium by increasing basolateral membrane [Cl.sup.-] conductance that permits [Cl.sup.-] exit after uptake via [Na.sup.+]-[K.sup.+]-2[Cl.sup.-] cotransport. potassium ion secretion; chloride secretion; epinephrine; prostaglandin [E.sub.2]; forskolin

PG[E.sub.2] is a proinflammatory mediator that can influence many cell types. This study was conducted to determine whether PG[E.sub.2] alters the electrical activity of distal colonic myenteric neurons, because colitis is typically associated with altered motility and changes in neural signaling may be involved. The electrical properties of intact myenteric neurons were evaluated with intracellular microelectrodes. Acute application of PG[E.sub.2] elicited a prolonged depolarization in both AH and S neurons with little effect on input resistance or electrical excitability. PG[E.sub.2] effects were suppreased by tetrodotoxin (TTX) or neurokinin (NK) receptor antagonists, indicating that PG[E.sub.2] acts directly and indirectly to depolarize colonic neurons. PG[E.sub.2]-evoked depolarization was concentration dependent (~3 [micro]M E[C.sub.50]) and was attenuated by the E prostanoid (EP)1/2 receptor antagonist, AH-6809. When preparations were maintained for 48 h in the presence of the stable PG[E.sub.2] analog PG[E.sub.2]-ethanolamide (10 [micro]M), neurons exhibited a significant membrane depolarization and enhanced excitability. These results suggest that PG[E.sub.2] can play a role in altered motility in colitis by evoking changes in the electrical properties of myenteric neurons. motility; inflammation; colitis; innervation; enteric nervous system

ATP-sensitive [K.sup.+] channels composed of Kir6.1 and SUR2B subunits in guinea pig gastric myocytes. Am J Physiol Gastrointest Liver Physiol 282: G137-G144, 2002; 10.1152/ ajpgi.00057.2002.--This study was designed to identify the single-channel properties and molecular entity of ATP-sensitive [K.sup.+] ([K.sub.ATP]) channels in guinea pig gastric myocytes with patch-clamp recording and RT-PCR. Pinacidil and diazoxide activated [K.sub.ATP] currents in a glibenclamide-sensitive manner. The open probability of channels was enhanced by the application of 10 [micro]M pinacidil from 0.085 [+ or -] 0.04 to 0.20 [+ or -] 0.05 (n = 7) and was completely blocked by 10 [micro]M glibenclamide. Single-channel conductance was 37.3 [+ or -] 2.5 pS (n = 4) between -80 and -20 mV in symmetrical [K.sup.+] gradient conditions. In inside-out mode, [K.sub.ATP] channels showed no spontaneous openings and were activated by the application of nucleotide diphosphates to the cytoplasmic side. These single-channel properties are similar to those of the nucleotide diphosphate-dependent [K.sup.+] channels in vascular smooth muscle, which are composed of Kir6.1 and sulfonylurea receptor (SUR)2B. RT-PCR demonstrated the presence of Kir6.1, Kir6.2, and SUR2B in guinea pig stomach smooth muscle cells. These results suggest that [K.sub.ATP] channels in smooth muscle cells of the guinea pig stomach are composed of Kir6.1 and SUR2B. adenosine 5'-triphosphate-sensitive potassium channels; Kir6.1-sulfonurea receptor 2B; smooth muscle cells; guinea pig stomach

Pinus ponderosa needle (PN) ingestion by late pregnant cows results in decreased uterine blood flow, premature parturition, and retained placentae. Further, plasma from PN-fed cows increases caruncular arterial tone (i.e., induces prolonged contraction) in an isolated perfused bovine placentome. A novel class of vasoactive lipids was isolated and identified using a bovine placentome assay-guided fractionation of [CH.sub.2][Cl.sub.2] extracts of PN. Placentome perfusion tests indicated that 1-12-dodecanedioyl-dimyristate (14-12-14) was the most potent of the PN lipids for increasing caruncular arterial tone. Late pregnant guinea pigs (GP) were used to evaluate the abortifacient activity of these vasoactive lipids. In Study 1, on d 50 of gestation, part of the control diet was replaced with chopped PN (Diet A) or chopped PN subjected to sequential extraction with diethyl ether ([Et.sub.2]0; Diet B); [Et.sub.2]0 and [CH.sub.2][Cl.sub.2] (Diet C); and [Et.sub.2]0, [CH.sub.2][Cl.sub.2], and methanol (Diet D). The GP on Diets A and B exhibited shorter (P < .01) gestation lengths and reduced (P < .01) pig birth weights than GP on the control diet or Diets C and D. Further, only GP on Diets A and B exhibited retained placentae. In Study 2, on d 50 of gestation, part of the control diet was replaced with chopped PN that had been subjected to exhaustive [CH.sub.2][Cl.sub.2] extraction and then infiltrated with either [CH.sub.2][Cl.sub.2] alone (Diet E), [CH.sub.2][Cl.sub.2] containing 14-12-14 (Diet F), or [CH.sub.2][Cl.sub.2] containing isocupressic acid (Diet G); then solvents were evaporated. The GP consuming Diet F had shorter (P < .05) gestation lengths and reduced (P < .05) pig birth weights than did GP consuming Diets E or G. The GP consuming Diet F also exhibited a high incidence of retained placentae. These data provide evidence that a unique class of vasoactive lipids in PN exhibit abortifacient activity in guinea pigs. Key Words: Lipids, Parturition, Placental Retention, Guinea Pigs

Research was conducted to examine the presence and the influence of prejunctional beta-2-adrenoceptors using electrical field stimulation of epithelium-denuded intact guinea pig tracheal tube preparations. Evoked endogenous acetylcholine and norepinephrine release were measured directly. Results demonstrate a differential capacity and response time profile of facilitatory prejunctional beta-2-adrenoceptors on adrenergic and cholinergic nerve terminals in the guinea pig trachea which illustrates the susceptibility of the receptors on adrenergic nerves to desensitization.

Research was conducted to examine the effects of opioids on cigarette smoke-induced plasma exudation in vivo in the anesthetized guinea pig bronchi using Evans blue dye as a plasma marker. The objective was to determine whether the opioid receptor-selective agonists or morphine inhibited cigarette smoke-induced plasma exudation. Results indicate that cigarette smoke-induced mu-opioid-receptor agonists inhibit cigarette smoke-induced plasma exudation in the bronchi of guinea pigs in vivo.

The Gram-positive bacterium Metabacterium polyspora is an uncultivated symbiont of the guinea pig gastrointestinal tract. Here we present evidence that in M. polyspora vegetative cell division has taken on a minor, and apparently dispensable, role in propagation. Instead, this unusual bacterium has evolved the capacity to produce progeny in the form of multiple endospores. Endospore formation is coordinated with transit of the bacterium through the gastrointestinal tract of the guinea pig. For the majority of cells, sporulation is initiated in the ileum, whereas later stages of development take place in the cecum. We show that multiple endospores are generated both by asymmetric division at both poles of the cell and by symmetric division of the endospores at an early stage of their development. Our findings suggest that M. polyspora represents an intermediate step in the evolution of a novel mode of cellular propagation that originates with endospore-forming Bacillus and Clostridium spp., which reproduce by binary fission, and extends to Epulopiscium spp., which create multiple viviparous offspring by a process of internal reproduction.

Research was conducted to examine the role of K+(sub ATP) channel inhibition on total and regional vascular resistance in guinea pig pregnancy. Equal numbers of pregnant and nonpregnant pigs were administered with glibenclamide, a K+(sub ATP) channel inhibitor. Blood flows, vascular resistance and blood pressure were compared before and after treatment with glibenclamide and after treatment during ANG II infusion. Results indicate that K+(sub ATP) has an effect on the regional control of vascular resistance during the pregnancy of guinea pigs.

Experiments were performed to investigate the relationship between the increased permeability of the tracheal mucosa in guinea pigs to horseradish peroxidase (HRP) following their exposure to ozone. The tracheal mucosa did not undergo significant morphological change after ozone exposure. However, pretreatment with capsaicin inhibited the increase in the permeability of the tracheal mucosa following ozone exposure. The findings confirmed that a 30 minute exposure to 3 ppm of ozone can increase the permeability of the tracheal mucosa in guinea pigs.