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Objectives: In the present study, effects of 3′,4′-dihydroxyflavonol (DiOHF) on anxiety-like behavior, and learning and memory were investigated in a model of transient global cerebral ischemia and reperfusion. Methods: The animals were assigned to sham-operated, ischemia, and two DiOHF-treated (10 mg/kg i.p.) groups. DiOHF was administered at 1 hour before and immediately after the ischemia. Male rats were subjected to bilateral common carotid artery occlusion to induce acute cerebral ischemia for 20 minutes, followed by reperfusion for 7 days. The openfield, elevated plus maze (EPM), and Morris water maze tests were used to evaluate the effects of DiOHF treatment on ischemia-induced locomotor activity, anxiety-like behavior, and spatial and recognition memory impairments, respectively. Results: In the open field test, locomotor activity in the ischemic rats was not altered 6 days after the ischemia, nor was anxiety-like behavior, which was evaluated with the EPM (P > 0.05). In the water-maze test, cerebral ischemia significantly decreased the exploration time in the target quadrant, and the platform crossing counts were lower (P < 0.05) in the probe trial test; this memory impairment was significantly improved by DiOHF applied 1 hour before and immediately after ischemia (P < 0.05). Discussion: All together, these findings suggest that DiOHF reverses spatial learning and memory deficits resulting from transient global ischemia but has no significant effect on anxiety-like behavior. [ABSTRACT FROM AUTHOR]

The flow due to rotating surfaces in a cylindrical enclosure is commonly used in many applications such as rheometry, electronic cooling, and turbo machinery, and has drawn scientists' attention for many years. The main objective of this study is to solve the problem with a robust and efficient code. It is achieved by using the 'Portable, Extensible Toolkit for Scientific computation' (PETSc), which is a computational tool for the parallel solution of scientific problems. By keeping the Newton's method as the non-linear solver, different linear solvers, preconditioning techniques, and numbers of processors are tested for the performance. In addition to computational parameters such as the performance of the linear solver, performance of the preconditioner, parallel performance, and grid dependence, the effects of some physical parameters such as the Reynolds number, aspect ratio, and altering of the rotating surface are investigated. The results indicate that the core of the circulation moves towards the stationary boundaries and the boundary layers become thinner with the increasing Reynolds number. Furthermore, decreasing the aspect ratio makes diffusion harder and lowers the maximum velocities. Some of the results are compared with data in the literature. [ABSTRACT FROM AUTHOR]

Mediastinal fat has been suggested to be associated with cardiovascular diseases such as carotid stiffness, atherosclerosis and coronary artery calcification. We investigated the possible role of Ad-36-induced obesity in the pathogenesis of the coronary artery disease (CAD). Ad-36 DNA was investigated in the anterior mediastinal fat tissue samples of obese adults with CAD. Seventy-five obese adults with left main coronary artery (LMCA) disease, 28 non-obese adults with valvular heart diseases, and 48 healthy individuals without cardiovascular problems were included as the obese patient group (OPG), non-obese patient group (NOG) and healthy control group (HCG), respectively. We also simultaneously investigated Ad-36 antibodies by serum neutralization test (SNA), and measured leptin and adinopectin levels. Ad-36 antibodies were detected only in 10 patients (13.3%) within the 75 OPG. A statistically significant difference was detected between OPG, NOG and HCG in terms of Ad-36 antibody positivity (p>0.05). Ad-36 DNA was not detected in mediastinal tissue samples of OPG and NOP without PCR inhibitors. We suggest that Ad-36 may not have an affinity for mediastinal adipose tissue in obese patients with left main CAD and valvular heart diseases. Ad-36 antibody positivity results are not sufficient to reach a causal relationship.

Moderate hypothermia (25-31 °C) may have a significant influence on vascular tone. At present, very little is known about the role of endothelial nitric oxide on the hypothermia-induced responses. In this study, we investigated the effect of hypothermia (to 28 °C) on the vasodilatation induced by verapamil, a phenylalkylamine calcium channel blocker (10 -9 -3 × 10 -4  M) and dihydropyridines, amlodipine (10 -9 -3 × 10 -4  M), and benidipine (10 -9 -10 -3  M) on 5-hydroxytryptamine (5-HT or serotonin) precontracted calf cardiac veins. Furthermore, the role of nitric oxide in the hypothermia-induced responses was analyzed. Ring preparations of veins obtained from calf hearts were suspended in organ baths containing 15 ml of Krebs-Henseleit solution, maintained at 37 °C, and continuously gassed with 95% O 2 -5% CO 2 . After a resting period, verapamil, amlodipine, and benidipine were applied cumulatively on serotonin (10 -6  M) precontracted calf cardiac vein rings and induced concentration-dependent relaxations. In another part of the study, the medium temperature was decreased to 28 °C after the preparations were contracted with 5-HT, then cumulative concentrations of verapamil, amlodipine, or benidipine were added. During hypothermia, the pIC 50 value, but not the maximal response, to all blockers were significantly higher than at 37 °C. Hypothermia in the presence of N G -nitro-l-arginine methyl ester (L-NAME, 10 -4  M) decreased the pIC 50 and E max values to verapamil, amlodipine, and benidipine. Only one blocker was tested in each preparation. These results suggest that nitric oxide may play a role in the hypothermia-induced changes in vasodilation caused by verapamil, amlodipine, and benidipine in calf cardiac vein, but further research is needed to explain the complete mechanism.

Opportunistic infections such as cryptosporidiosis and cyclosporiasis are commonly encountered in patients with acquired immunodeficiency syndrome (AIDS). We investigated the existence of opportunistic protozoans that significantly affect the quality of life in HIV-1 infected patients using conventional and molecular methods. The study group comprised 115 HIV-1 positive patients. In the identification of Cyclospora cayetanensis and Cryptosporidium, the formol-ether precipitation method was used and smears were evaluated in optical microscope by staining modified Ziehl-Neelsen (ZN). The primers and probes used for PCR were Heat shock protein 70 for C. cayetanensis and the oocysts wall protein for Cryptosporidium spp.. Cyclospora and Cryptosporidium spp. oocysts were detected in one and two patients, respectively, by staining, whereas we detected C. cayetanensis in three patients out of 115 (2.6%) by PCR, and Cryptosporidium spp. in a further three patients (2.6%). C. cayetensis was detected in patients with CD4 counts of 64 cells/μm, 182 cells/μm and 287 cells/μm, respectively. Cryptosporidium spp. was detected in patients with CD4 counts of 176 cells/μm, 241 cells/μm and 669 cells/μm. As conclusion, PCR method is faster and more sensitive than microscopic methods and to screen intestinal pathogens routinely in patients infected with HIV should not be neglected in developing countries like Turkey.

Adenovirus 36 (Ad-36) has recently been suggested as a possible contributor to the current obesity epidemic. The aim of this study was to investigate the prevalence of Ad-36 antibodies in obese children, as well as investigate the role of serum leptin and lipid levels in Ad-36-obesity. Seventy-one obese children and 62 non-obese children were included as the patient group (PG), including the healthy control group (HCG), respectively. Simultaneously, Ad-36 antibodies and adipokine levels were assessed with serum neutralization assays (SNA) and ELISA. Ad-36 antibody was detected in 9 patients (12.7%) and 1 patient (1.6%) in both the PG and HCG, respectively, while a significant difference was detected between groups (p < 0.05). Although serum LDL, total cholesterol, triglycerides and leptin levels were detected significantly higher, adiponectin level was detected paradoxically lower in the PG. However, a significant difference was not detected for lipids and leptin levels; adiponectin levels were found to be significantly lower in Ad-36 antibody-positive PG (p < 0.05). In conclusion, we suggest there is an association between Ad-36 and obesity in children, including IL-6 levels increasing in obese children with Ad-36 seropositivity. Conversely, adiponectin levels in obese children with Ad-36 seropositivity were higher. As such, there is a need for studies to understand the mechanisms underlying this observation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The effects of moderate hypothermia (28 °C) on the response of human varicose spermatic vein to α 1 -adrenoceptor agonist phenylephrine and the role of endothelial nitric oxide (NO) in these effects were studied. Concentration-response curves for phenylephrine (10 -9 to 3 × 10 -4 M) were recorded in rings with and without endothelium at 37 and 28 °C. To further analyze the role of NO, in the response to phenylephrine during hypothermia, the effects of this agonist in the presence of N G -nitro-L-arginine methyl ester (10 -4 M) were also determined. Under every condition tested, phenylephrine produced a marked, concentration-dependent contraction. Sensitivity of intact veins to the agonist was consistently lower at 28 °C than at 37 °C. There was no significant difference in phenylephrine response at 28 and 37 °C in vessels without endothelium but at 28 °C veins without endothelium showed a higher sensitivity than intact veins to phenylephrine. The sensitivity of veins with and without endothelium to nitroprusside (10 -9 to 3 × 10 -3 M) was significantly decreased during hypothermia, and endothelium removal did not affect the relaxation to this nitrovasodilator. These results suggest that moderate hypothermia decreases the sensitivity of human varicose spermatic vein to phenylephrine probably by increasing the availability of endothelial NO.

Objective: The effects of Rho-kinase inhibitors on vasodilatation induced by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor rosuvastatin (10-9-10-4M) on 5-HT-precontracted calf cardiac vein and the role of endothelium in these effects were analyzed., Material and Methods: Cardiac vein ring preparations were suspended in organ baths containing 25 ml of Krebs-Henseleit solution, maintained at 37 °C and continuously gassed with 95% O2-5% CO2. At the end of the resting period, the cardiac vein preparations were contracted with 10(-6) M 5-HT. After the contraction had reached a steady state, rosuvastatin was added to the organ bath cumulatively (10(-9)-10(-4) M)., Results: Rosuvastatin relaxed the cardiac vein rings in general while the degree of relaxation was greater in those with endothelium and lower in those without it. HA1077 [1-(5-isoquinolinesulfonyl)-homopiperazine] (Fasudil, 10(-6) M) and Y-27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide dihydrochloride] (10(-6) M) incubation increased the rosuvastatin-induced relaxation only in the presence of endothelium., Conclusions: The results demonstrate for the first time that in calf cardiac vein, rosuvastatin induced endothelium-dependent relaxations while Rho-kinase inhibition increased these relaxations in the presence of endothelium layer (Fig. 3, Ref. 44).

Objective: At present, very little is known about the effects of donepezil on vascular reactivity. The aim of the present study was to evaluate the responses of rat urinary bladder to donepezil (10-10-3x10-4 M) and the role of Spirulina supplementation in these effects., Material and Methods: Animals were divided into the two groups of six animals in each group. The first group received only distilled water daily as vehicle for six weeks and served as the control. The second group received Spirulina 750 mg kg -1 orally, daily for six weeks and served as the spirulina group. Preparations of rat urinary bladder were used from both groups., Results: Donepezil produced concentration dependent relaxation of rat urinary bladder preparations pre-contracted with KCl.The pIC50 value, but not the maximal response of donepezil, was significantly lower (p<0.05) in the Spirulina supplemented group., Conclusions: These results demonstrated for the first time that spirulina treatment can affect urinary bladder activity (Fig. 1, Ref. 20).

Objective: At present very little is known about the role of endothelial nitric oxide (NO) in the effects of temperature on vascular reactivity. The aim of the present study is to evaluate the influence of cooling (to 28 °C) on the vasodilatation induced by cilostazol(10-9-3x10-4M) on carbachol (10-6)-precontracted calf cardiac vein and coronary artery and the role of NO in these effects., Materials and Methods: Ring preparations of great cardiac vein and the anterior interventricular branch of left coronary artery were used., Results: Cilostazol produced concentration-dependent relaxation of calf cardiac vein and coronary artery rings precontracted with carbachol. During cooling, the pIC50 values, but not the maximal responses to cilostazol were significantly lower than at 37 °C in both preparations. Cooling to 28 °C in the presence of NG-nitro-L-arginine methyl ester (L-NAME, 10-4 M) did not modify the effect of temperature both in cardiac vein and coronary artery. These results demonstrate for the first time that cooling-induced changes of cilostazol in calf cardiac vein and coronary artery are independent of NO (Tab. 2, Fig. 3, Ref. 32).

The main objective of the study was to investigate the effects of age and sex differences on locomotor activity, learning and memory in rats. Another objective was to investigate whether repeated elevated plus maze tests induce anxiety in rats. Eighty Wistar rats were divided into eight groups according to their sex, age and anxiety status. Locomotor activity was assessed in open field. Repeated anxiety tests were performed in elevated plus maze. Spatial learning and memory were evaluated with the Morris water maze. All behavioral tests were recorded online and analyzed offline with an analytical software. Exploratory behavior was lower in anxiety-induced rats. Male rats had lower anxiety levels, locomotor activity and exploratory behavior compared to females. During the training period of Morris water maze latency to find platform, total distance traveled and average swimming speed decreased in all groups with repeated tests and young rats generally were faster than aged rats. During the probe trial, although the number of platform crossings was not affected, time spent in the platform zone was higher in the young groups compared to the aged groups. In conclusion, age and sex affect locomotor activity, learning and memory in different aspects., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Increased generation of oxidants and (or) reduced endogenous antioxidant defense mechanisms are associated with the etiology of diabetic vascular complications. The aim of the present study was to evaluate whether curcumin supplementation increases the vasodilatory effect of cilostazol in streptozotocin induced diabetic rat aorta. Cumulative addition of cilostazol caused concentration-dependent relaxations of thoracic aorta rings. The sensitivity and the maximal response to cilostazol were significantly higher in control than those in diabetic animals. Treatment with curcumin in control rats increased the sensitivity to cilostazol. Further, in aortic rings from diabetic rats treated with curcumin, the responses to cilostazol were significantly increased in comparison to the response in aorta from untreated diabetic rats. It can be conclude, that curcumin increases the cilostazol-induced vasodilation in diabetic rat aorta.

Background: Curcumin is an antioxidant molecule that has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In the present study, we aimed to evaluate the possible effects of curcumin on contractile response to agonists and histopathological alterations in rat esophagus subjected to mesenteric I/R., Materials and Methods: Adult male Wistar albino rats were randomly allocated to 4 groups, namely group I: sham-operated animals (n=10); group II: animals subdued to I/R injury only (n=10) and laparotomy; 45 minutes of superior mesenteric artery ligation were followed by 2 hours of reperfusion, group III: curcumin/sham (n=10); 20 days before I/R, curcumin (200 mg/kg/) was administered by gastric gavage, and group IV: curcumin-I/R (n=10). Mesenteric ischemia/reperfusion model was generated by clamping the superior mesenteric artery for 45 min followed by reperfusion for 2 h. Oral administration of curcumin by gavage at a dose of 200 mg/kg/day lasted 20 days just before inducing the mesenteric ischemia. At the end of reperfusion period, all animals were sacrificed and esophagus samples were collected to assess the contractile response to agonists and histopathological alterations., Results: Ischemia/reperfusion significantly decreased the contractile responses to carbachol and KCl and this decrease was attenuated by curcumin. Pretreatment with curcumin caused a remarkable decrease in histopathological parameters such as edema, congestion and inflammatory cells., Conclusions: The results of the present study demonstrate for the first time that curcumin can attenuate the esophageal injury associated with I/R (Tab. 4, Fig. 3, Ref. 32).

Cisplatin-based chemotherapy has a variety of vascular side effects. The aim of the present study was to evaluate the beneficial effect of melatonin and cisplatin on the alterations in vascular reactivity and structure of cisplatin-treated rats. Phenylephrine (PHE) and KCl-caused concentration-dependent contractions of rat aorta. Pretreatment with cisplatin increased the sensitivity but not the max response to PHE and KCl. In rats treated with melatonin or quercetin before cisplatin, the EC50 values, but not the maximal response to both agents were significantly higher than cisplatin-treated group. Compared to the control group, cisplatin-treatment significantly reduced the luminal area of the aorta. In melatonin and quercetin-treated aortas the luminal area values were significantly higher than cisplatin-treated group. The results demonstrate for the first time that melatonin and quercetin treatment may protect the aorta in cisplatin-based chemotherapy.

The effects of melatonin and quercetin on the contractile responses of cisplatin-treated rat detrusor smooth muscle were tested. Detrusor strips obtained from four separate rat groups (control, cisplatin, melatonin+cisplatin and quercetin+cisplatin) were mounted in 25 mL organ baths containing Krebs-Henseleit solution (KHS) at 37°C, continuously gassed with 95% O₂ and 5% CO₂. The vasoconstriction induced by acetylcholine (ACh) and potassium chloride (KCl) were compared within the groups. Furthermore, histopathological parameters such as edema, congestion, inflammatory cells, microvascular proliferation, fibrosis, eosinophil, mast cells and epithelial damage were noted. In routine experiments ACh and KCl triggered concentration-dependent contractions. Pretreatment with cisplatin increased the sensitivity but not the maximal response to ACh and KCl. In rats treated with melatonin or quercetin before cisplatin, the EC₅₀ values, but not the maximal response, to both agents were significantly higher than in the cisplatin-treated (CII) group. Histopathological parameters such as edema, congestion, inflammatory cells, microvascular proliferation, fibrosis, eosinophil, mast cells and epithelial damage were all higher in the cisplatin-treated group than in the controls. Melatonin pretreatment significantly decreased mast cell numbers and epithelial damage when compared to cisplatin treatment alone but these effects were not recorded with quercetin pretreatment. These results demonstrate for the first time that melatonin can attenuate urinary bladder injury produced by cisplatin treatment., (Copyright 2010 Prous Science, S.A.U. or its licensors. All rights reserved.)

The effects of cooling (to 28 degrees C) and warming (to 41 degrees C) on the vasoconstrictions induced by 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) and the role of nitric oxide in these effects were analyzed in human umbilical artery and vein. 5-HT (10(-9)-10(-4) M) and ACh (10(-9)-10(-4) M) induced concentration-dependent contractions at 37, 28 and 41 degrees C. During cooling, the sensitivity, but not the maximal response, of 5-HT and ACh was significantly higher than at 37 degrees C; and during warming, again the sensitivity, but not the maximal response, of both contractile agents was significantly lower than at 37 degrees C. Neither cooling to 28 degrees C nor warming to 41 degrees C, after treatment with N(G)-nitro-L-arginine methyl esther (L-NAME, 10(-4) M), modify the effect of temperature in both vessels. These results suggest that cooling- and warming-induced responses in human umbilical artery and vein are independent of nitric oxide.

The effects of cooling (to 28 degrees C) on histamine (10(-9) - 3 x 10(-4) M)-induced contractions and the role of calcium (Ca(2+)), potassium (K(Ca) (2+)) and sodium (Na(+)) channel blockers in the cooling-induced responses were investigated in the endothelium-denuded human umbilical artery. Concentration-response curves to histamine were isometrically recorded at 37 and 28 degrees C (control). The same procedure was repeated at 28 degrees C in the presence of tetraethylammonium (TEA, 10(-3) M), pilsicainide (10(-6) M), ouabain (10(-6) M), caffeine (3 x 10(-4) M), verapamil (10(-6) M) and also in Ca(2+)-free medium with ethylene glycol bis-(beta-aminoethyl ether) N,N,N(1),N(1)-tetraacetic acid (EGTA). During cooling, the sensitivity, but not the maximal response, was significantly higher than 37 degrees C. Cooling to 28 degrees C after treatment with verapamil or pilsicainide decreased the sensitivity, whereas treatment with TEA and ouabain significantly increased sensitivity. Treatment with caffeine did not modify the effect of cooling. Furthermore, cooling to 28 degrees C after incubation in Ca(2+)-free solution with EGTA decreased the sensitivity to histamine. The results of this study suggest the role of Ca(2+), K(Ca) (2+) and Na(+)-ion channels in the cooling-induced changes of human umbilical arteries treated with histamine.

The effects of warming (to 41 degrees C) on the serotonin (5-HT, 10(-8)-3 x 10(-3) M)- and carbachol (10(-)9-3 x 10(-4) M)-induced contractions and the role of calcium (Ca2+), potassium (K+), and sodium (Na+) channel blockers, in the warming-induced responses were investigated in the calf cardiac vein. Concentration-response curves to 5-HT and carbachol were isometrically recorded at 37 and 41 degrees C (control). The same procedure was repeated at 41 degrees C in the presence of verapamil (10(-6) M), caffeine (3 x 10(-4) M), tetraethylammonium (TEA, 10(-3)M), flecainide (10(-6) M), and also in the Ca2+-free medium with ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA). During warming, the sensitivity, but not the maximal response, was significantly higher. Warming to 41 degrees C after treatment with verapamil or flecainide decreased the sensitivity, whereas treatment with caffeine increased the sensitivity significantly. Treatment with TEA did not modify the effect of warming. Furthermore, warming to 41 degrees C after incubation in Ca2+-free solutions with EGTA decreased the sensitivity to 5-HT and carbachol. The results of this study suggest the role for Ca2+ and Na+ ions in the warming-induced changes of cardiac vein treated with 5-HT and carbachol.

Objective: To determine the myocardial and vascular effects of remifentanil and fentanyl in human atria and saphenous veins., Design: In vitro, prospective with repeated measures., Setting: University research laboratory., Interventions: The direct effects of remifentanil and fentanyl on the electrical stimulation-induced contraction of nonfailing human atrium and saphenous veins contracted with 5-hydroxytryptamine were studied., Measurements and Main Results: In human atrial trabeculae, cumulative (10(-9)-10(-5) mol/L) added remifentanil had no effect on contractile force, compared with untreated muscles (p > 0.05). The force of contraction was significantly less than control values with concentrations of fentanyl ranging from 10(-8) to 10(-5) mol/L (p < 0.05). At the highest concentration (10(-5) mol/L), the inhibition by fentanyl of the electrical stimulation-induced contraction was 40.6% +/- 6.32%. In human saphenous vein strips preconstricted with 5-hydroxytryptamine, remifentanil (10(-8)-10(-5) mol/L) and fentanyl (10(-8)-10(-5) mol/L) produced "concentration-dependent" relaxation when compared with the control contraction value (p < 0.05). The IC(50) was similar with remifentanil and fentanyl and the E(max) of fentanyl was significantly higher than remifentanil (p < 0.05). The venodilatory effects of remifentanil and fentanyl were similar on veins with or without endothelium (p > 0.05)., Conclusions: Remifentanil has no direct effect on the contraction of myocardium. Fentanyl inhibits the electrical stimulation-induced contraction in human right atrial muscles in vitro. Remifentanil and fentanyl produce "concentration-dependent" relaxation in human saphenous vein strips independent from the endothelium.

The effects of warming on the response to various contractile agents of calf cardiac vein were studied using 2.5-mm long cylindrical segments. Concentration-response curves for carbachol (10(-9)-3 x 10(-4) m), 5-hydroxytryptamine (5-HT; 10(-8)-3 x 10(-3)), potassium chloride (KCl; 10(-4)-5 x 10(-2) m) and calcium chloride (CaCl2; 10(-4)-10(-2)) were isometrically recorded at 37 and 41 degrees C (warming). During warming the sensitivity, but not the maximal response, of carbachol 5-HT, KCl, and CaCl2 was significantly higher than at 37 degrees C. Warming to 41 degrees C after treatment with NG-nitro-L arginine methyl esther (10(-5) m) did not modify the effect of warming. These results suggest that nitric oxide seems to have no role in the warming-induced responses in calf cardiac vein.

The role of K+ ions on the vasoconstrictions induced by carbachol during cooling (28 degrees C) in the endothelium of a denuded calf coronary artery and cardiac vein (noncutaneous vessel) was studied. Carbachol (10(-9) - 3 x 10(-4) M) induced concentration-dependent contractions at both 37 degrees C and 28 degrees C. The sensitivity, but not the maximal response, of carbachol (10(-9) -3 x 10(-4) M) was significantly lower at 28 degrees C than at 37 degrees C. Cooling to 28 degrees C after treatment with tetraethylammonium (TEA, 10(-3) M) or ouabain (10(-5) M), after incubation in K+-free medium increased the sensitivity to carbachol in both preparations. The results suggest a role for K+ ions in the cooling-induced changes of noncutaneous vessels.

The aim of the present study was to investigate the possible role of nitric oxide (NO) as a nonadrenergic, noncholinergic (NANC) mediator in human colon smooth muscle in vitro and to examine its possible interactions with K+ channels. In the presence of atropine (10(-6) M) and guanethidine (10(-5) M), electrical field stimulation (EFS, 1-10 Hz, 0.3 msec, 50 V) for 10 sec induced relaxations which were inhibited by tetrodotoxin (10(-6) M). In the presence of NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), relaxations induced by EFS at 1, 2, 4, 8 and 10 Hz were reduced by 38.7 +/- 4.3, 31.5 +/- 3.8, 54.3 +/- 5.4, 59.8 +/- 4.5 and 68.6 +/- 5.3%, respectively. The relaxations inhibited by L-NAME were restored by the preincubation of L-arginine (L-ARG, 10(-3) M) at all frequencies tested. D-Arginine (D-ARG, 10(-3) M) had no effect. Tetraethylammonium (TEA, 10(-4) M) or glibenclamide (10(-6) M) significantly decreased the relaxations induced by EFS. Exogenously applied sodium nitroprusside caused concentration-dependent relaxation with maximum relaxation observed with 10(-3) M. TEA (10(-4) M) and glibenclamide (10(-6) M) significantly depressed the maximum response to sodium nitroprusside. In conclusion, our data indicate that NO is involved in NANC nerve-mediated relaxation in the human colon smooth muscle and the relaxant responses to endogenously released or exogenously applied NO are mediated, in part, by activation of calcium-dependent and ATP-sensitive K+ channels.

The interaction of the alpha 2-adrenoceptor agonists clonidine and xylazine with the alpha 1-adrenoceptors in the rat and rabbit aortas was investigated. In preparations preconstricted with phenylephrine (10(-6) M), cumulative addition of clonidine and xylazine induced concentration-related vasodilatation in the presence of the alpha 2-adrenoceptor antagonist yohimbine and the beta-blocker propranolol. Neither clonidine nor xylazine treatment inhibited 5-HT- and KCl-induced vasoconstriction. It is concluded that alpha 2-agonists have affinity for alpha 1-adrenoceptors in rat and rabbit aortas.

In the present study, nonadrenergic, noncholinergic (NANC) responses of rabbit detrusor smooth muscle and the possible involvement of the L-arginine/nitric oxide (L-ARG/NO) pathway was investigated. In the presence of atropine (10(-6) M) and guanethidine (10(-5) M), frequency-response curves were obtained by stimulating tissue with 10-sec trains at increasing frequencies (1-10 Hz) with 3-min intervals between stimulations. Electrical field stimulation (EFS) evoked a biphasic response in rabbit detrusor smooth muscle, consisting of an initial contraction followed by relaxation. ATP desensitization significantly inhibited contractions. L-NAME (10(-5) M) increased the contractions by a maximum of 33 +/- 5% at 1 Hz, 37 +/- 5% at 2 Hz, 18 +/- 4% at 4 Hz, 20 +/- 3% at 8 Hz and 15 +/- 4% at 10 Hz. In detrusor preparations, exposure to L-NAME (NG-nitro-L-arginine methyl ester, 10(-5) M) significantly reduced the maximal relaxation to electrical stimulation to 7 +/- 3% of the control. In the presence of L-ARG (10(-4) M), contractions induced by electrical field stimulation (EFS) at 1, 2, 4, 8 and 10 Hz were reduced by 20 +/- 4, 24 +/- 3, 25 +/- 3, 20 +/- 3 and 30 +/- 5%, respectively. Exposure to L-ARG (10(-4) M) significantly increased the maximal relaxation to electrical stimulation to 52 +/- 5% of the control. Exogenously applied ATP (10(-5)-10(-2) M) to rabbit detrusor muscle resulted in contractions while sodium nitroprusside (10(-7)-10(-3) M) caused concentration-dependent relaxation. These results suggest that nitric oxide (NO) acts as an inhibitory NANC neurotransmitter in the rabbit detrusor smooth muscle. Additionally, NANC contractions mediated by ATP released from NANC nerves, may be masked by the L-ARG/NO pathway in this tissue.