title: Relaxant properties mediated by nitroglycerin in aortic coarctation hypertensive rats.
abstract: Nitroglycerin-mediated vasorelaxation is chiefly attributed to the cyclic guanosine monophosphate (cGMP)-dependent pathway, and partly to the cGMP-independent pathway via calcium-activated K(+) channels (K(Ca)). To investigate whether chronic hypertension alters responses of vascular smooth muscle to vasoactive agonists, we determined nitroglycerin-mediated relaxation of aortic rings from coarctation hypertensive rats. Banding the abdominal aorta above the renal arteries for 4 weeks elevated blood pressure and caused cardiac hypertrophy by 49%. In response to nitroglycerin, the relaxation of aortic rings precontracted with 10(-7) M norepinephrine was lower in the banded group than in the sham-operated group. Methylene blue, a guanylate cyclase inhibitor, suppressed a greater part of nitroglycerin-mediated relaxation and reached similar levels of relaxation in the two groups. Charybdotoxin, a specific K(Ca) channel blocker, also suppressed the relaxation by about 40% in the aortic rings from sham-operated animals, but not in those from the banded group. The response to charybdotoxin was markedly diminished or virtually eliminated in the banded group in the presence or absence of methylene blue. The combination of charybdotoxin and methylene blue nearly abolished nitroglycerin-mediated relaxation in the sham-operated group, whereas nitroglycerin-mediated relaxation was seen to remain in the banded group. These results indicate that the involvement of cGMP-independent K(Ca) channels in nitroglycerin-mediated relaxation disappeared after the development of hypertension produced by aortic coarctation.
authors.affiliation: Internal Medicine II, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsui
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Fukami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Saburi
authors.forename: Hajime
authors.initials: H
authors.lastname: Iami
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Mizuno
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishimoto
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000503:physiopathology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001017:Aortic Coarctation / Q000188:drug therapy* / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006339:Heart Rate / Q000187:drug effects; D006838:Hydrocarbons; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008697:Methane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000098:blood supply* / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D006838:Hydrocarbons; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D018999:Charybdotoxin; C030011:carbene; D005996:Nitroglycerin; D008697:Methane; D009638:Norepinephrine