N-acetylcysteine ameliorates chemotherapy-induced impaired anxiety and depression-like behaviors by regulating inflammation, oxidative and cholinergic status, and BDNF release.

Mood disorders caused by chemotherapy have become more important as the survival of cancer patients increases, and new studies in this field will contribute to the prevention of this disorder. For this purpose, we used methotrexate, a chemotherapeutic agent frequently preferred in oncological cases. Mtx was administered as a single dose of 100 mg/kg intraperitoneally to male Wistar albino rats. Since oxidative stress plays an important role in chemotherapy-induced emotional impairment, n-acetylcysteine (NAC), a potent antioxidant, was administered at 500 mg/kg in two doses before Mtx administration. We evaluated anxiety and depression-like behaviors 24 h after Mtx administration, as well as some oxidative and inflammatory markers in blood serum and hippocampal tissue, acetylcholinesterase activity (AChE), and brain-derived neurotrophic factor (BDNF) release in hippocampal tissue. In rats, Mtx induced anxiety and depression-like behaviors as well as abnormalities in oxidative and inflammatory markers in blood serum and hippocampal tissue, increased AChE activity in hippocampal tissue, and decreased BDNF release. NAC treatment was found to ameliorate Mtx-induced anxiety and depression-like behaviors, increase antioxidant capacity, reduce oxidative stress and inflammatory response, and regulate AChE activity and BDNF release. In conclusion, the fact that NAC treatment of Mtx was effective is important for revising the treatment strategies for individuals suffering from this disorder, and this effect is thought to be related to the antioxidant and anti-inflammatory power of NAC.

Moderate hypothermia and responses to calcium channel blockers - Role of the nitric oxide.

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% O2-5% CO2. 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 pIC50 value, but not the maximal response, to all blockers were significantly higher than at 37 °C. Hypothermia in the presence of NG-nitro-l-arginine methyl ester (L-NAME, 10-4 M) decreased the pIC50 and Emax 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.

Neopterin and soluble CD14 levels as indicators of immune activation in cases with low anti-HCV reactivity and true HCV infection.

Neopterin and soluble CD14 (sCD14) are detected at high levels in hepatitis C virus (HCV) infections. We aimed to evaluate the role of these plasma immune activation biomarkers, for the indirect assessment of immune activation status of patients with low anti-HCV reactivity and a HCV infection. Low anti-HCV reactivity group (LRG, n: 70), true positive HCV infection group (THG, 30) and healthy control group (HCG, 30) were analyzed in this study. We have used ELISA, HCV RIBA/LIA and HCV-RNA methods. Mean neopterin levels were significantly lower in LRG than THG (p <0.001). In contrast, those values were not significantly different from those of HCG (p >0.05). Mean sCD14 were significantly higher in LRG than THG and HCG (p <0.05, p <0.001). Values of 3.95 µg/ml and 5.36 nmol/l for sCD14 and neopterin resulted in the maximum area under the receiver operating characteristic curves (ROC), which were 0.859 (95% CI, 0.745 to 0.935; <0.0001) and 0.788 (95% CI, 0.663 to 0.883; <0.0001), respectively. These cut-offs corresponded to a sensitivity of 73.3% and a specificity of 73.3% for neopterin and of 100% and 76.7% for sCD14. Our results suggest that a specific immunoactivation might be caused by true positive HCV infection. Due to the significant results sCD14 in LRG might be non-specifically affected by some underlying atypical immunohematological pathologies. Only neopterin might be used to exclude low anti-HCV reactivity from a true HCV infection. The use of neopterin but not sCD14 in combination with fourth-generation EIA/CMIA combo tests will be useful when nucleic acid tests are not available for screening blood donors at blood banks.

Cilostazol enhances atorvastatin-induced vasodilation of female rat aorta during aging.

Statins have cholesterol-independent effects including an increased vascular nitric oxide activity and are commonly used by patients with cardiovascular disease. Such patients frequently have cardiovascular diseases, which may be treated with cilostazol, a platelet aggregation inhibitor. This study was designed to investigate whether combined use of cilostazol would increase the inhibitory effect of statin on vascular smooth muscle and how maturation would affect these responses. Female Wistar rats, aged 3-4 months (young) and 14-15 months (adult), were sacrificed by cervical dislocation and the thoracic aorta was dissected and cut into 3- to 4-mm-long rings. The rings were mounted under a resting tension of 1 g in a 20-ml organ bath filled with Krebs-Henseleit solution. Rings were precontracted with phenylephrine (10-6 M), and the presence of endothelium was confirmed with acetylcholine (10-6 M). Then, the concentration-response curves were obtained for atorvastatin alone (10-10 to 3 × 10-4 M; control) and in the presence of cilostazol (10-6 M) in young and adult rat aortas. This experimental protocol was also carried out in aorta rings, which had been pretreated with NG-nitro-l-arginine methyl ester (l-NAME, 10-4 M). Atorvastatin induced concentration-dependent relaxations in young and adult rat thoracic aorta rings precontracted with phenylephrine. The pIC50 value of atorvastatin was significantly decreased in adult rat aortas. In addition, pretreatment of aortas with cilostazol enhanced the potency of atorvastatin in both young and adult aortas. Incubation with l-NAME did not completely eliminate the relaxations to atorvastatin in the presence of cilostazol. These results suggest that combined application of cilostazol with atorvastatin was significantly more potent than atorvastatin alone. Combined drug therapy may be efficacious in delaying the occurrence of cardiovascular events.

3',4'-Dihydroxyflavonol attenuates spatial learning and memory impairments in global cerebral ischemia.

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.

Moderate hypothermia attenuates α1-adrenoceptor-mediated contraction in human varicose spermatic vein: The role of nitric oxide(Short communication).

The effects of moderate hypothermia (28 °C) on the response of human varicose spermatic vein to α1-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 NG-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.

Rosuvastatin-induced responses in calf cardiac vein.

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).

Curcumin alleviates cisplatin-induced learning and memory impairments.

The present study has been designed to investigate the role of curcumin on cisplatin-inducedcognitive impairment and to reveal mechanisms of cisplatin's detrimental actions on cognition in rats. Animals were treated with cisplatin (5mg/kg/week) and/or curcumin (300mg/kg/day) for 5weeks. Morris water maze test was used to assess spatial learning and memory. Enzymatic activities of acetylcholinesterase (AChE) and superoxide dismutase (SOD) were evaluated from hippocampus and plasma samples, and malondialdehyde (MDA), which is the end-product of lipid peroxidation, was determined by a colorimetric method. Our results showed that cisplatin (5mg/kg/week, 5weeks) caused learning and memory deficits, elevated MDA content, decreased SOD activity in the hippocampus and plasma, and AChE activity in the hippocampus. Curcumin improved learning and memory in rats with administration of cisplatin. In addition, curcumin significantly reduced the level of MDA and increased the activities of SOD and AChE. Taken together, our findings indicate that curcumin ameliorates cisplatin-induced spatial learning and memory impairment, possibly through restored cholinergic function and enhanced oxidative status.

Cilostazol-induced relaxation of calf cardiac vein and coronary artery during cooling.

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).

Donepezil-induced response of Spirulina supplemented rat urinary bladder.

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).

Age and sex affect spatial and emotional behaviors in rats: the role of repeated elevated plus maze test.

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.

Role of curcumin in mesenteric ischemia - reperfusion injury in rats.

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).

Curcumin increases vasodilatory effect of cilostazol in diabetic rat aorta.

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.

Effects of treatment with coenzyme Q10 on exercised rat aorta.

In this study, the effect of long-term supplementation of coenzyme Q10 (CoQ10) on the responses of swim-trained rat aorta was investigated. Twenty-four adult male Wistar rats were divided into four groups: untrained, trained, untrained+CoQ10, and trained+CoQ10 group. In the trained groups rats swam for 60 min/day, five days/week for six weeks. The CoQ10 supplements were administered by intraperitoneal injection at a daily dose of 10 mg·kg-1 of body weight five days/week for six weeks. Swimming of the rats was performed in a container containing tap water. Rats were sacrificed and thoracic aortas were removed for ex vivo analysis after the last swimming session. The aortas were cut into rings 2.5 mm in length. Concentration-response curves for phenylephrine (PHE, 10-9-3×10-4 M) and potassium chloride (KCl, 5-100 mM) were isometrically recorded. The sensitivity and maximal responses to PHE and KCl of aortic rings obtained from trained rats were lower than those of untrained rats. CoQ10 supplementation decreased the responses to both vasoconstrictors in untrained and especially in trained groups. Although neither CoQ10 nor training did affect malondialdehyde (MDA) and protein carbonyl (PC) levels, creatine kinase (CK) activity decreased and superoxide dismutase (SOD) activity increased only with exercise training. Glutathione (GSH) levels increased in CoQ10 supplemented-untrained rats. In conclusion, our results suggest that CoQ10 supplementation may have beneficial effects during exercise.

Role of the nitric oxide on relaxation of the human umbilical artery during cooling.

In the present study, the effects of cooling (to 28°C) on the vasodilatation induced by diazoxide (10(-9)-3×10(-4) M), isoproterenol (10(-9)-3×10(-4) M) and magnesium sulphate (0.1-30 mM) on serotonin-pre-contracted human umbilical artery and the role of nitric oxide in these effects were analyzed. Diazoxide, isoproterenol and magnesium produced concentration-dependent relaxation of human umbilical artery precontracted with serotonin (10(-6) M). During cooling, the pIC(50) values and maximal responses to these agents were significantly lower than at 37°C. Cooling to 28°C in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) did not modify the effects of temperature on diazoxide, isoproterenol and magnesium-induced relaxations. These results suggest that cooling-induced changes of diazoxide, isoproterenol, and magnesium sulphate in human umbilical artery are independent of nitric oxide.

Alpha lipoic acid treatment improved endothelium-dependent relaxation in diabetic rat aorta.

The aim of this study was to ascertain the effects of α-lipoic acid (ALA) treatment on relaxant responses of acetylcholine (ACh) and isoprenaline (ISO) in aortic rings precontracted with serotonin (5-HT, 10(-6) M) obtained from streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in the rats by 50 mg/kg streptozotocin (STZ) via an intraperitoneal injection. Rat body and aorta weights were measured. The isometric tension to ACh (10(-9)-3×10(-6) M) and ISO (10(-9)-10(-4) M) of 5-HT-precontracted diabetic and non-diabetic rat (control), diabetic-ALA-treated, and ALA-treated aortas, in organ baths were recorded. Six weeks after STZ treatment blood glucose was elevated compared to control rats. In aortic rings from diabetic rats ACh and ISO-induced relaxations were impaired whereas endothelium-independent relaxation to sodium nitroprusside (SNP) was unaffected. ALA (100 mg/kg/day) treatment for 5 weeks enhanced ACh and ISO-induced relaxation in diabetic aortas. This recovering effect was via NO because prevented by incubating the vessels with N(G)-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). It may be assumed that ALA treatment in vivo, can protect against impaired vascular responsiveness in STZ-induced diabetic rats.

Response to vasoconstrictor agents by detrusor smooth muscles from cisplatin-treated rats and antioxidant treatment.

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.

Vasoprotection by melatonin and quercetin in rats treated with cisplatin.

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.

Role of the nitric oxide on diazoxide-induced relaxation of the calf cardiac vein and coronary artery during cooling.

The effects of cooling (to 28 degrees C) on the vasodilation induced by diazoxide (10(-9)-3 x 10(-4) M) on carbachol-pre-contracted calf cardiac vein and coronary artery and the role of nitric oxide in these effects were analyzed. Diazoxide produced concentration-dependent relaxation of calf cardiac vein and coronary artery rings pre-contracted with carbachol (10(-6) M). During cooling, the pIC(50) values, but not the maximal responses, to diazoxide were significantly lower than at 37 degrees C in both preparations. Cooling to 28 degrees C in the presence of N(G)-nitro-L-arginine methyl ester (10(-4) M) did not modify the effect of temperature both in cardiac vein and coronary artery. These results suggest that cooling-induced changes of diazoxide in calf cardiac vein and coronary artery are independent of nitric oxide.

Effects of cooling and warming on 5-hydroxytryptamine- and acetylcholine-induced contractions of human umbilical vessels: role of nitric oxide.

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.