Cilazapril reverses endothelium-dependent vasodilator response to acetylcholine in mesenteric artery from spontaneously hypertensive rats.
This study was designed to evaluate the effect of chronic treatment with cilazapril on vascular reactivity of aorta and mesenteric artery from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Cilazapril (5 mg/kg), an angiotensin converting enzyme inhibitor, was injected intraperitoneally twice a day for 4 weeks. Results demonstrated that acetylcholine (ACh)-induced relaxation in aorta and mesenteric artery from SHR was significantly less than that from WKY, cilazapril-treated WKY, and SHR. The impairment of ACh-induced relaxation in SHR was significantly reversed after cilazapril treatment and there were no significant differences among WKY, cilazapril-treated WKY, and SHR. Meanwhile, both N omega-nitro-L-arginine (LNNA; 10(-4) mol/L) and methylene blue (MB; 10(-5) mol/L) completely blocked the vasodilator response to ACh in aorta but only partly inhibited in mesenteric artery from WKY, cilazapril-treated WKY, and SHR. These LNNA- and MB-resistant vasodilator responses to ACh in mesenteric artery were only slightly inhibited by TEA (10(-3) mol/L) but not by indomethacin (5 x 10(-6) mol/L). These findings suggest that there may be an unidentified endothelium-dependent relaxing factor(s) (EDRF), which exists in the endothelium and may participate in the modulation of blood pressure in SHR. Results further demonstrate that the antihypertensive effect of cilazapril may be partly mediated by the reversing function of endothelium to release EDRF and LNNA-resistant, unidentified relaxing factor(s).
Department of Pharmacology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Republic of China, Taiwan.
R H
RH
Young
Y A
YA
Ding
Y M
YM
Lee
M H
MH
Yen
D000109:Acetylcholine / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D017315:Cilazapril; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine