Benidipine improves endothelial function in renal resistance arteries of hypertensive rats.
We studied the effects of long-term antihypertensive treatment on endothelial function in renal resistance arteries from spontaneously hypertensive rats (SHR). Wistar-Kyoto rats (WKY) were used as a normotensive reference. Adult SHR were treated with benidipine (a calcium antagonist) or ecarazine (a vasodilator) for 10 weeks; the drugs caused similar reductions in blood pressure. Changes in isometric tension of rings prepared from the third-order branches of the renal arteries were recorded. Endothelium-dependent relaxations induced by acetylcholine in rings contracted with norepinephrine were smaller in SHR than in WKY. The impaired relaxation was improved by benidipine treatment, but ecarazine had no significant effect. In vitro treatment with meclofenamic acid, a cyclooxygenase inhibitor, did not alter the differences in the relaxations. In the presence of meclofenamic acid, N omega-nitro-L-arginine methyl ester slightly reduced the relaxations; the relaxation was smaller in SHR than in WKY and was not affected by benidipine treatment. In rings contracted with 40 mmol/L. KCI, the relaxations induced by acetylcholine in the presence of meclofenamic acid were smaller than those in rings contracted with norepinephrine. The relaxation was smaller in SHR than in WKY but was normalized by benidipine treatment. Thus, acetylcholine relaxes rat renal resistance arteries by releasing nitric oxide and endothelium-derived hyperpolarizing factor from the endothelium, which is impaired in SHR. Long-term benidipine treatment improves the impaired relaxation in SHR by enhancing nitric oxide-mediated relaxation.
Dohi
Y
Y
Second Department of Internal Medicine, Nagoya City University Hospital, Japan.
Kojima
M
M
Sato
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors; D014032:Todralazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014655:Vascular Resistance
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009569:Nitric Oxide; C061004:benidipine; D000109:Acetylcholine; D014032:Todralazine