Modulation by aging of the coronary vascular response to endothelin-1 in the rat isolated perfused heart.
Changes with age in the coronary vascular response to endothelin-1 were investigated in perfused hearts isolated from 2-, 6- and 24-month-old (mo) male Fisher-344 rats. Endothelin-1 injected as a single bolus (0.3, 3 and 30 nmol) into the coronary artery supply caused dose-dependent vasoconstriction in all three age groups. While there was no age-related change in the vasoconstriction induced by the lower doses (0.3 and 3 nmol), the higher dose (30 nmol) elicited a more pronounced vasoconstriction in 6- and 24-mo rats than that in 2-mo rats. NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide formation, markedly enhanced the vasoconstriction induced by 30 nmol endothelin-1 in 2- and 6-mo rats but only slightly and non-significantly enhanced that vasoconstriction in 24-mo rats. Haemoglobin, which inhibits activation of guanylate cyclase by nitric oxide, enhanced the endothelin-1-induced vasoconstriction in 2-mo rats, but not in 6- and 24-mo rats. The acetylcholine-induced coronary vasodilation was more pronounced in 2- and 6-mo rats than in 24-mo rats and was attenuated by L-NNA in 2- and 6-mo rats. The coronary vasodilation induced by nitroprusside (0.1 mmol), a pharmacological precursor of nitric oxide, did not change with age. Endothelin-1 (30 nmol) markedly increased the release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in all three age groups. The prostaglandin synthesis inhibitor indomethacin enhanced the endothelin-1-induced vasoconstriction in 2- and 6-mo rats to a similar extent.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Yamagata University School of Medicine, Japan.
Y
Y
Katano
A
A
Ishihata
S
S
Morinobu
M
M
Endoh
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology*; D006454:Hemoglobins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344
D016232:Endothelins; D006454:Hemoglobins; D011453:Prostaglandins; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine