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Urinary bladder distension is known to influence the cardiovascular system under a pathophysiological condition such as spinal cord injury, hypertension, and arteriosclerosis. A reflex due to bladder distension and/or contraction is considered as one reason for the cardiovascular disturbance associated with micturition. However, it has remained unknown how much intravesical pressure (IVP) rises during micturition in daily life and to what extent mean arterial blood pressure (MAP) and heart rate (HR) respond at that time. To answer these questions, we attempted to examine the direct changes in IVP, MAP, and HR during natural micturition in freely moving conscious rats. IVP increased from the baseline value of 4 +/- 0.2 mmHg to 14 +/- 0.5 mmHg during natural micturition. Although MAP and HR began to increase before micturition, the increases in MAP and HR became significant 1-4 s before its onset. The peak increases in MAP and HR (7 +/- 0.8 mmHg and 14 +/- 3 beats/min, respectively) were delayed by 2 s from the peak IVP. Following an administration of xylocaine into the urinary bladder, the increases in MAP and HR during micturition were significantly blunted to 5 +/- 2 mmHg and 8 +/- 3 beats/min, although IVP increased the same as it did during micturition without xylocaine. Moreover, the relationship between IVP and MAP or HR during natural micturition resembled that between IVP and the vesico-cardiovascular reflex responses during isovolumic bladder contraction in anesthetized rats. Therefore it is concluded that natural micturition in freely moving conscious rats accompanies the significant cardiovascular responses despite a limited increase in intravesical pressure, to which a reflex from the urinary bladder may substantially contribute.

We investigated the neural regulation of the cardiac interval to an exercise demand signal and to a repeated exercise in 20 healthy human subjects. Electrocardiogram (ECG), muscle torque, and electromyogram (EMG) were simultaneously measured and their time relationships compared before and during the exercise. The R-R interval of ECG was directly increased by the exercise demand signal itself before the onset of EMG but not reflexly by muscle contraction. The cardiac interval decreased at the onset of exercise. Under the condition of repeated maximum eccentric training, the resting cardiac interval decreased prior to the exercise, whereas the brief increase in cardiac interval to the exercise demand signal remained unchanged. These results suggested that when autonomic nerve activity to the pacemaker is activated by the exercise demand signal, an initial effect of vagal nerve activity appears, and an effect of vagal nerve withdrawal and/or sympathetic nerve activity then appears. The responses of the heart and leg skeletal muscle at the onset of exercise are not synchronized, and the cardiac interval is controlled by vagal and sympathetic nerve activities to effect a transition to a high heart rate as quickly and smoothly as possible.

We measured internal diameter (ID) changes in resistance and conduit pulmonary arteries of 1- and 2-week hypoxic rats and normoxic control rats in response to nitric oxide synthase (NOS) inhibitors in vivo. At 2 weeks of hypoxic exposure, the ID reduction as a result of NOS inhibition was enhanced within the resistance arteries, but not at 1 week of hypoxia.

To improve cardiac adjustment to exercise, we developed a new self-biofeedback heart rate (HR) controller. Using this device, we analyzed time courses of HR, running speed (RS), stride length (ST) and pitch of gait (PI) in response to various preset HR levels in 7 normal human subjects. When HR was preset at 80 bpm, HR increased rapidly in response to exercise and exceeded the preset level at 12. 1 s with overshoot. At the preset HRs of 100, 120, 140 and 160 bpm, the HRs increased to each preset level at 39.2, 64.5, 58.5 and 83.0 s after the onset of exercise, respectively, and the HRs were adjusted with a range of +/- 4%. For all preset HRs, RS, ST and PI increased more rapidly than the HR and reached the maximum values within 30 s. During exercise, RS, ST and PI remained constant within 1.5-5.5 min. HR, RS, ST and PI increased in proportion to the preset HR. The increases in PI against HR (DeltaPI/DeltaHR) decreased with the higher HR level, and at HRs of 160-170 bpm, HR and PI showed identical rhythm. The increases in RS were produced by 18-59% increases in PI and by 12-44% increases in ST. We concluded that, using our newly developed self-biofeedback HR control system, we could control HR to a given preset value by a change in RS due to PI and ST.

Using an X-ray television system on anesthetized cats, we directly measured internal diameter (ID) changes in identical small pulmonary vessels (100-1,100 microm ID) in response to inhalations of 25, 250, and 2,500 ng/kg/min aerosolized prostacyclin (PGI2), 4 and 34 ppm nitric oxide (NO), and the combination of aerosolized PGI2 and NO. We also compared ID changes during 250 ng/kg/min PGI2 inhalation both with and without an Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg I.V.) pretreatment. In the arteries, inhaled PGI2 increased 100-900 microm vessel ID in a dose-dependent manner but caused no significant, or only slight, ID increases in the vessels larger than this. The greatest ID increase ( approximately 22%) was in the 100-500 microm arteries in response to 2,500 ng/kg/min PGI2 inhalation. PGI2 also increased the ID of the veins (6-12%), but the results were not dose related. NO inhalation also resulted in non-uniform ID response patterns similar to PGI2 with no significant, or only minimal, ID increases of the arteries >900 microm. The simultaneous inhalation of 2,500 ng/kg/min PGI2 and 34 ppm NO increased the arterial ID (maximum approximately 34%) more than either drug alone and to almost the same extent as brought about by injected papaverine (2 mg/kg), a smooth muscle relaxant. Inhaled PGI2 (250 ng/kg/min) decreased pulmonary arterial pressure and increased arterial ID to nearly the same extent with or without L-NAME pretreatment. These results indicate that inhaled PGI2 and inhaled NO locally dilate 100-900 microm pulmonary arteries in a dose-dependent manner and with a similar ID response pattern, and that the combination of these drugs produces a more enhanced vasodilator effect compared to their separate effects and induces the maximum dilated states. The data also suggest that inhaled PGI2 dilates these arteries directly, rather than via secondary release of endogenous NO.

The aim of this work was to examine whether endothelium-derived relaxing factor (nitric oxide) mediates cat hindlimb cholinergic vasodilation induced by stimulation of the posterior hypothalamus and beta-adrenergic vasodilation by I.V. injection of isoproterenol using an inhibitor of nitric oxide synthesis, NW-nitro-L-arginine methyl ester (L-NAME). Without L-NAME, femoral blood flow velocity (FBV) increased during hypothalamic stimulation by 11.2 +/- 2.2 cm/s (mean +/- SEM) from the baseline value of 8.4 +/- 2.2 cm/s and femoral conductance (FC) increased by 0.084 +/- 0.021 cm/s/mmHg from 0.062 +/- 0.016 cm/s/mmHg, which were abolished by atropine (0.5 mg I.A.). Arterial blood pressure (AP) and heart rate (HR) increased during hypothalamic stimulation (15 +/- 8 mmHg and 22 +/- 6 beats/min). When isoproterenol (1-2 micrograms I.V.) was injected, FBV and FC increased 5.1 +/- 0.56 cm/s and 0.048 +/- 0.005 cm/s/mmHg. With L-NAME (20-100 mg I.A.), the rises in AP and HR during hypothalamic stimulation were unchanged but the increases in FBV and FC were significantly blunted to 5.2 +/- 3.7 cm/s and 0.026 +/- 0.021 cm/s/mmHg. In contrast, L-NAME did not affect the responses in FBV and FC during stimulation of beta-adrenergic receptors. The effect of NG-monomethyl-L-arginine (10-30 mg I.A.) was the same as L-NAME. It is suggested that nitric oxide is involved in hindlimb cholinergic vasodilation neurally induced by hypothalamic stimulation but not in beta-adrenergic vasodilation.

Using an X-ray television system, we directly measured the changes in internal diameter (ID; 100-600 microns) of small pulmonary arteries and veins in response to intravenous infusion of atrial natriuretic peptide (ANP) in anesthetized rabbits and cats. Under physiological conditions, ANP (0.01-1 micrograms/(kg.min) for 3 min) increased the ID of the small arteries in a dose-dependent manner by 4-9% and by 6-14% in the rabbit and cat, respectively. The maximum increase in ID occurred in the 400-600 microns arteries. In the small veins, however, the peptide had no significant effects on the ID. To simultaneously investigate the ANP-induced responses of pulmonary vessels with different vascular tone in a given lung region, we embolized a part of the rabbit pulmonary vascular tree with micro-beads (80-100 microns diameter) and measured ID responses to ANP (1 microgram/(kg.min) for 3 min) in the embolized vessels with elevated tone and the nonembolized vessels with baseline tone. In the embolized arteries, which had constricted by 31%, ANP induced 27% increase in ID, while in the nonembolized arteries it caused 8% increase in ID. This indicated that in the small arteries, the vasodilator activity of ANP is greatly enhanced under the conditions of elevated vascular tone. In the small veins, however, no significant vasodilation occurred even under the elevated-tone conditions. We concluded that ANP dilates the arterial segments in the rabbit and cat pulmonary microcirculation selectively and in a dose-dependent manner. Furthermore, the pulmonary vasodilator effect of ANP was dependent on the pulmonary vascular tone.

Acute elevations in left atrial pressure (LAP) were induced by altering the volume of air within a balloon inserted into the left atrium; the changes in internal diameter (ID) of small muscular pulmonary arteries (100-600 microns ID) in response to the associated rises of pulmonary arterial pressure (PAP) were measured using an X-ray TV system on the in vivo cat lung. When LAP was elevated to 14 +/- 1, 24 +/- 1, and 30 +/- 1 mmHg, PAP was increased to 21 +/- 1, 30 +/- 1, and 37 +/- 1 mmHg, respectively. With PAP ranging from 16 (control value) to 21 mmHg the ID did not dilate significantly. With PAP of 30-37 mmHg significant ID dilation occurred. The magnitude of the ID dilation (16%) with PAP of 37 mmHg, however, was significantly smaller than that (20%) with PAP of 30 mmHg despite the greater pressure rise. When the elevated PAP of 30-37 mmHg was quickly returned to the control level by rapid balloon deflation, the ID constricted significantly below the control level. The magnitude of the ID constriction was proportional to the degree of the preceding PAP rise and was maximal in the arteries of 200-400 microns ID. A papaverine hydrochloride injection combined with the balloon deflation completely abolished the ID constriction. A phentolamine injection, on the other hand, significantly attenuated the constriction with approximately half of the constriction persisting. The results indicate that an increase in vascular smooth muscle tone occurred in the small muscular pulmonary arteries, particularly those of 200-400 microns ID, in response to the acute rise of PAP above 30 mmHg during the LAP elevation. In addition, the data suggest the partial participation of catecholamines in the active contraction of vascular smooth muscle. The arterial contraction may serve to protect the pulmonary capillaries from an excessive hydrostatic pressure and pulmonary edema.

Using a new X-ray TV system, we studied the effects of metabolic acidosis, produced by intravenous injection of lactic acid, on internal diameter (ID; 100-500 micron), flow velocity, and volume flow in pulmonary microcirculation of anesthetized cats. We found that metabolic acidosis decreased the ID of arteries by 21%, whereas it increased flow velocity by 28% but not volume flow.

Time courses of heart rate (HR), arterial pressure (AP), and head movement at the beginning of eating were analyzed in conscious cats. The cats were trained to eat when movements of their body trunks were restrained. Food was presented for 10 sec at intervals of 100 sec. With the abrupt presentation of food, a head-down movement occurred immediately and thereafter eating started with a mean latency of 1.6 sec. During eating HR increased by 22% from the preeating value and AP was elevated by 11%. To determine the time relation between the onset of eating and the change in each variable in response to eating, mean time courses of HR, AP, and head movement were obtained from 7-40 trials in each cat. The head-down movement preceded the onset of eating by 1.3 sec. The increase in HR preceded the onset of eating by 0.2 sec; the change in AP followed it by 3-4 sec. This indicated that the increase in HR was not induced reflexly either by food intake or by the change in AP. After administration of hexamethonium, the changes in HR and AP in response to eating were abolished, although eating was evoked by the food presentation. Additionally, the increase in HR was also reduced by propranolol and atropine. Thus, the acceleration of HR at the beginning of eating may be induced by central activation of the autonomic nervous system.

Using X-ray angiography, the internal diameter (ID) of 31 sites of arteries in the hindlimb, i.e., the iliac, main femoral, profundal femoral, circumflex femoral, saphenous, and popliteal arteries, was measured in anesthetized rabbits. ID under the control condition was 294-1,796 micrometers, but was changed to 376-1,828 micrometers, 127-1,914 micrometers, and 423-2,098 micrometers with administration of hexamethonium bromide, noradrenaline, and phentolamine, respectively. The constrictor effects of noradrenaline and plasma catecholamine were larger in the femoral artery than in the iliac artery. At the transition site from the iliac to the femoral artery, ID per unit length increased from 190 micrometers/10 mm in the control to 320 micrometers/10 mm with noradrenaline. The constrictor effects of sympathetic nerve activity (SNA) on the profundal femoral, circumflex femoral, saphenous, and popliteal arteries varied among 19 out of 20 sites. Plasma catecholamine constricted ID at 18 sites but dilated it at 2 sites. Noradrenaline constricted ID at all 20 sites, particularly in the popliteal and saphenous arteries. It was concluded that the effects of SNA and plasma catecholamine on ID on rabbit hindlimb arteries were qualitatively and quantitatively non-uniform among different arteries and at different sites of the given artery.

The effects of baroceptor reflex on mean cardiac (MCSNA) and renal sympathetic nerve activity (MRNA) were analyzed before and after atropinized (0.1 mg/kg, i.v.) states in conscious cats at rest. Resting values of MCSNA, MRNA, mean aortic pressure (MAP), and heart rate (HR) were 85 +/- 6 imps/s, 76 +/- 11 imps/s, 100 +/- 4 mmHg, and 164 +/- 10 beats/min, respectively. Both MCSNA and MRNA changed almost inversely to changes in the absolute MAP in the range of 90-140 mmHg. Within this pressure range the gain of baroceptor-sympathetic system to the heart and kidney was 2.31 and 1.84, respectively. MCSNA as well as MRNA was reduced to the noise level at the MAP of 142 and 150 mmHg, respectively. With atropine, MCSNA and MRNA were inhibited centrally whereas HR increased to 192 beats/min. The increase in MAP caused by norepinephrine (2.1 micrograms/kg, i.v.) was enhanced to 75 +/- 7 mmHg by atropine from 31 +/- 4 mmHg in control. The piecewise linear MAP-MCSNA and MAP-MRNA relationships changed to a remarkable clockwise hysteresis loop. During the rising MAP period, the gain of the baroceptor-sympathetic system decreased to 0.91 and 0.97 in MCSNA and MRNA, respectively. During the returning MAP period, a delayed activation in MCSNA and MRNA occurred centrally. We conclude that the baroceptor reflex effect on MCSNA is larger than those on MRNA, and that the baroceptor control of MCSNA and MRNA is modified centrally by atropine in the awake cat at rest.

We recorded renal nerve activity (RNA) together with arterial pressure (AP) and heart rate (HR) in 24 Wister rats anesthetized with nitrous oxide to investigate the effects of ketamine on the sympathetic nerve activity and the cardiovascular dynamics. The magnitude and time course of the responses to four graded doses of ketamine (1, 5, 10, 25 mg/kg) were studied in 19 rats. RNA responded biphasically, initially decreasing dose-dependently to minimal values of 89 +/- 4.4, 77 +/- 8.2, 54 +/- 5.2, and 17 +/- 3.7% of control for 1, 5, 10, and 25 mg/kg, respectively, and then increasing above control dose-independently. AP showed a biphasic response. HR first decreased dose-dependently but then increased slightly. In the remaining five rats, we compared the effects of ketamine 5 mg/kg on RNA, AP, and HR before surgical baroceptor denervation with those after the denervation. The denervation abruptly increased RNA, AP, and HR. Ketamine decreased RNA, AP, and HR in the denervated state and returned them to pre-ketamine values without overshoot. The finding that in the nerve intact state ketamine produced the characteristically biphasic response of RNA could be explained by the following mechanisms: (1) ketamine depresses the vasomotor center causing the initial decrease in RNA; (2) ketamine depresses the inhibitory effects of baroreflex causing the successive increase in RNA. The biphasic change in AP could be partly attributed to biphasic responses of RNA to ketamine.

Left ventricular systolic pressure volume area (PVA) has been reported to be a reliable predictor of cardiac oxygen consumption rate per beat (VO2) in a given heart with a stable inotropic background. PVA has been defined as the specific area in the pressure-volume (P-V) plane that is bounded by the end-systolic and end-diastolic P-V relationship lines and the systolic segment of the P-V loop trajectory. In the present experimental study, we separated PVA into two parts: EW and PE. EW is the area surrounded by the P=V loop, corresponding to the external mechanical work. PE is the area surrounded by the end-systolic and end-diastolic P-V lines and the relaxation segment of the P-V loop, corresponding to what is considered the end-systolic elastic potential energy in terms of a time-varying elastance model of the ventricle. We attempted to find an optimal weighting coefficient K of PE for the best correlation between VO2 and PVAW = EW + K . PE, changing K from 0 to infinity. Results in 7 canine excised cross-circulated hearts showed that PVAW best correlated with VO2 at K = 1.03 +/- 0.03 (SE). Since PVAW at K = 1 is identical with the original PVA, we concluded that PVA could serve as a reliable predictor of VO2. PVA is concluded to be physiologically significant in the coupling between cardiac mechanics and energetics.

Cardiac sympathetic nerve activity (CSNA in imp/s) was measured in the postganglionic fibers of awake cats at rest, during body movement, and with excitement. The CSNA showed synchronized discharges with various periodicities. Rhythms of the synchronized CSNA were analyzed by an interval histogram (IIH). The IIH showed a multimodal distribution. The first model interval (Tc) was in a range of 75 to 125 ms. An 8-12 cycle/s Tc rhythm, i.e., inverse value of Tc, was always observed in the awake cat at rest and during body movements. Probability of the 8-12 cycle/s Tc rhythm was smallest at rest, increased during body movement, and was largest with excitement. These results suggested that the 8-12 cycle/s Tc rhythm, observed in all states in the conscious cat, is a fundamental rhythm of central cardiovasomotor origin. The subsequent model distribution (Tb = 2 x Tc, 3 x Tc, 4 x Tc, or 5 x Tc) ranged from 150 to 700 ms, mostly 200 to 500 ms. A 2-5 cycle/s Tb rhythm, i.e., inverse value of Tb, appeared more frequently at rest than that during body movement or with excitement. A new model concerning a mechanism to cause the 2-5 cycle/s Tb rhythm is suggested.

This study was undertaken to scrutinize the difference in the response of cardiac sympathetic nerve activity (CSNA) and renal nerve activity (RNA) to coronary artery occlusion. The magnitudes and time courses of per cent changes in CSNA and RNA, recorded simultaneously in 22 dogs, were compared with each other during a 1 min occlusion of the left circumflex coronary artery under four different conditions. With afferent nerve intact, changes in CSNA and RNA showed similar biphasic patterns comprising initial increases (CSNA, 9 +/- 3.1% (S.E.); RNA, 16 +/- 6.4%, at 20 sec of occlusion) and subsequent decreases (CSNA, -3 +/- 4.3%; RNA, -11 +/- 6.5%, at 60 sec), despite the progressive fall in arterial pressure (from 109 +/- 4 to 89 +/- 4 mmHg). After carotid sinus denervation, the initial increases in both nerve activities were reduced and the subsequent decreases became more evident. The decreases in RNA (-47 +/- 8.0%) were significantly greater than those in CSNA (-23 +/- 5.6%). After bilateral cervical vagotomy, changes in both CSNA and RNA showed in contrast similar monophasic increasing patterns (CSNA, 18 +/- 4.0%; RNA, 25 +/- 5.6%, at 60 sec), where RNA increased more than did CSNA. After carotid sinus and vagoaortic denervation, CSNA and RNA increased only slightly throughout the occlusion. These results conclusively indicate that the reflex responses in CSNA and RNA during coronary occlusion are quantitatively different, though qualitatively similar, and that RNA is inhibited significantly more than CSNA by the reflex mediated through the afferent vagal nerves.

If a rest interval is applied to a regularly stimulated cardiac muscle, the first contraction after this interval (post-rest contraction) has either a greater (post-rest potentiation) or a smaller (post-rest inhibition) developed tension than the regular contraction. Positive inotropic interventions will augment the post-rest potentiation and reduce the post-rest inhibition. We examined the effects of muscle stretching on the post-rest contraction in papillary muscles isolated from adult cats and from kittens and compared the effects with those of two typical inotropic interventions: high frequency stimulation and high calcium concentration. We found that muscle stretching augmented the post-rest potentiation and reduced the post-rest inhibition in a manner similar to the two inotropic interventions in the adult cat papillary muscle, and that these effects were consistently reversed in the kitten papillary muscle. The similarity of the effect of muscle stretching to those of the two typical inotropic interventions in either adult cat or kitten papillary muscle suggests that the effect of muscle stretching is due to an inotropic effect of muscle length change.

Using a biotelemetry system, the electrocardiogram (ECG) was continuously measured over 24 hr in a given environmental condition in 8 normal human subjects. The frequency of ventricular excitation rhythm (VER) was obtained from inverse of R-R interval of ECG. This study was undertaken to be informed of the variation of VER over 24 hr in resting normal subjects with different ages. The averaged frequency of VER per day (VERd) and its relative coefficient of variation (CV) ranged from 1.44 to 1.01 Hz (mean: 1.24 Hz) and 26 to 10% (mean: 20%) with age of 10 to 73 years (mean: 42 years). VERd and CV showed a tendency to decrease with age. The VERd histogram showed not a normal distribution but a multimodal distribution. Two or three large positive deviations, denoted as L, N, and H modal components, from the normal distribution curve were detected. The mode of L and H modal components was 1.01 and 1.37 Hz, respectively. The frequency distribution of L and H modal components changed with relation to a circadian rhythm and sleep-wakefulness cycles. An hourly histogram of ventricular excitation rhythm (VERh) frequently showed an unimodal distribution and the relative coefficient of variation of VERh ranged from 7.9 to 13.3% which was smaller than that of CV. The mode of VERh histogram changed in association with the circadian rhythm, the sleep-wakefulness cycles and a fluctuation period of 2 to 3 hr.