Effect of captopril on acetylcholine-induced relaxation in the presence of nitroglycerin tolerance in isolated rabbit aorta.
We investigated the effects of angiotensin converting enzyme inhibitors on acetylcholine-induced endothelium-dependent vasodilation in the presence of nitroglycerin tolerance in rings of rabbit thoracic aorta mounted in tissue baths and precontracted with 10(-6) M norepinephrine. The vasorelaxant effects of acetylcholine were measured before and after 1 h treatment with 5 x 10(-4) M nitroglycerin. The acetylcholine dose-response curve shifted to the right after the induction of nitroglycerin tolerance. Pretreatment with captopril (a sulfhydryl angiotensin converting enzyme inhibitor), but not with M-1 (a metabolite of delapril and a nonsulfhydryl angiotensin converting enzyme inhibitor) restored acetylcholine-induced relaxation. Pretreatment with N-acetylcysteine also restored reduced acetylcholine-induced relaxation. These results suggest that the sulfhydryl group plays a major role in restoration of reduced acetylcholine-induced vasodilation in the presence of nitroglycerin tolerance.
Moroi
M
M
Third Department of Internal Medicine, Ohashi Hospital, Toho University School of Medicine, Tokyo, Japan.
Akatsuka
N
N
Fukazawa
M
M
Ishikawa
M
M
Aikawa
J
J
Namiki
A
A
Yamaguchi
T
T
D000109:Acetylcholine / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005996:Nitroglycerin / Q000008:administration & dosage*; D011817:Rabbits; D013438:Sulfhydryl Compounds; D014665:Vasodilator Agents / Q000008:administration & dosage*; D014666:Vasomotor System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D014665:Vasodilator Agents; D002216:Captopril; D005996:Nitroglycerin; D000109:Acetylcholine