thromboxane-a2 and benidipine

The effects of benidipine on contractions induced by contractile agents were studied in isolated dog basilar, middle cerebral and mesenteric arteries and compared with those of nicardipine. KCl (20-80 mM), U-46619 (3 x 10(-10)-3 x 10(-6)M) and 5-hydroxytryptamine (5-HT) (10(-9)-3 x 10(-6)M) produced concentration-dependent contractions in the three arteries. Benidipine (10(-11)-8 x 10(-9)M) inhibited non-competitively the KCl-induced contraction in the basilar, middle cerebral and mesenteric arteries with a pD'2 of 9.1, 9.7 and 8.5, respectively. There was a significant difference between the pD'2 values in the cerebral and mesenteric arteries. Benidipine (10(-6)-3 x 10(-5)M) attenuated significantly the contraction produced by both U-46619 and 5-HT in the three arteries, the pD'2 being 4.4-4.9. Nicardipine inhibited the contraction induced by the three contractile agents in the same manner as benidipine. The contraction caused by 70 mM KCl in the cerebral and mesenteric arteries was reduced by 33-38 and 18%, respectively following treatment with 0.25 mM Ca2+ solution. Furthermore, pretreatment with a Ca(2+)-free solution containing 1 mM EGTA inhibited KCl-induced contractions in the basilar, middle cerebral and mesenteric arteries by 98.7, 95.6 and 92.1%, respectively. It also attenuated the contractions produced by both 10(-6) M U-46619 and 3 x 10(-6) M 5-HT in the cerebral and mesenteric arteries by 56-61 and 34-39%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Calcium Channel Blockers; Cerebral Arteries; Dihydropyridines; Dogs; Female; In Vitro Techniques; Male; Mesenteric Arteries; Muscle Contraction; Muscle, Smooth, Vascular; Nicardipine; Potassium Chloride; Prostaglandin Endoperoxides, Synthetic; Serotonin; Thromboxane A2; Vasoconstrictor Agents

We investigated the possible protective effects of benidipine (Coniel), a calcium antagonist, on mechanical dysfunction, metabolic damage and changes in vascular reactivity during ischemia and reperfusion in the Langendorff-perfused rat heart. The responses of perfusion pressure to U-46619, a vasoconstrictor, and acetylcholine, an endothelial-dependent vasodilator, were also determined as indices of the vascular function. Thirty min of reperfusion following 30 min of global ischemia produced contractile failure and the marked release of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK). Additionally, the ischemia and reperfusion augmented the vasoconstrictor response to U-46619, and depressed the endothelium-dependent vasodilator response to acetylcholine. These hearts were treated with 1 or 10 nM benidipine from 20 min before ischemia to the beginning of ischemia. While benidipine at 10 nM had a modest negative inotropic action, 1 nM of this drug had minimal depressant effects on the preischemic function. The depressed contractile function after the ischemia was improved, and the increased releases of LDH and CPK were significantly ameliorated by benidipine. Also, benidipine restored the augmented contractile response to U-46619 and preserved the vasodilator response to acetylcholine. These results demonstrate that pretreatment with benidipine prevents myocardial injury following ischemia and reperfusion. The cardioprotective effects of benidipine may in part be due to the protection of vascular reactivity by this drug.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Animals; Calcium Channel Blockers; Dihydropyridines; Disease Models, Animal; In Vitro Techniques; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion Injury; Prostaglandin Endoperoxides, Synthetic; Rats; Rats, Wistar; Thromboxane A2; Vascular Resistance; Vasoconstrictor Agents