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).

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).

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).

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.

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).

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.

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.

Effects of cooling on histamine-induced contractions of human umbilical artery: the role of ion channels.

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.

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.

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.

Warming and response to contractile agents in calf cardiac vein: role of the Ca2+, KCa2+, and Na+ ion channel blockers.

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.

Warming and response to contractile agents in calf cardiac vein: role of the nitric oxide.

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.

Nonadrenergic, noncholinergic responses of the rabbit detrusor smooth muscle and the role of L-arginine/nitric oxide pathway in these responses.

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.

Interactions between phenylephrine, clonidine and xylazine in rat and rabbit aortas.

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.

Nonadrenergic, noncholinergic responses of the human colon smooth muscle and the role of K+ channels in these responses.

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 role of K+ ions on the response to carbachol of calf coronary artery and cardiac vein during cooling.

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.

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 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.