Nitroglycerin-induced aortic relaxation mediated by calcium-activated potassium channel is markedly diminished in hypertensive rats.
Nitroglycerin (NTG), a nitric oxide (NO) donor, is considered to relax vascular smooth muscle by stimulating soluble guanylate cyclase, which in turn increases cyclic GMP (cGMP) level. Recently it became evident that NO-induced vasodilatation is also mediated by stimulating Ca-activated K (K(Ca)) channels directly and/or indirectly through cGMP. We, therefore, tried to investigate the possible involvement or the alteration of K(Ca) channels in the mechanism of vasodilation induced by NTG in physiological and pathological conditions. Using rings prepared from thoracic aortas of spontaneously hypertensive rats (SHR) and those of age-matched Wistar-Kyoto rats (WKY), we studied changes in isometric tension of the rings in response to NTG to evaluate effects of a soluble guanylate cyclase inhibitor methylene blue (MB), and a specific blocker of K(Ca) channel charybdotoxin (CTX). Rings from WKY and SHR precontracted with norepinephrine showed similar aortic relaxation to NTG. MB markedly suppressed the NTG-induced relaxation in both strains, leaving about 30% of MB-resistant relaxation. CTX nearly completely eliminated this MB-resistant relaxation in WHY but did not affect this relaxation in SHR. These results suggest that NTG-induced vasorelaxation is mediated through i) cGMP-dependent and ii) cGM P-independent K(Ca) channel involving mechanisms, the latter may be diminished or virtually eliminated in hypertensive state.
Fukami
Y
Y
Internal Medicine II, Nagoya University School of Medicine, Japan.
Toki
Y
Y
Numaguchi
Y
Y
Nakashima
Y
Y
Mukawa
H
H
Matsui
H
H
Okumura
K
K
Ito
T
T
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D018999:Charybdotoxin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D018999:Charybdotoxin; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D002118:Calcium; D008751:Methylene Blue; D009638:Norepinephrine