Altered effect of cyclopiazonic acid on endothelium-dependent relaxation in femoral arteries from hypertensive rats.
The function of endoplasmic reticulum in hypertensive vascular endothelium has not been intensively studied. The current study was designed to investigate a role of intracellular Ca2+ stores in endothelium-dependent relaxations to acetylcholine using femoral arteries obtained from Wistar-Kyoto (WKYs) and spontaneously hypertensive rats (SHRs). Rings were prepared from the femoral arteries and changes in isometric tension were recorded. Endothelium-dependent relaxations induced by acetylcholine in rings contracted with serotonin were identical in WKYs and SHRs. Cyclopiazonic acid (CPA) inhibited the relaxation in SHRs but not in WKYs. In WKYs, acetylcholine evoked smaller relaxations in rings contracted with KCl than in those contracted with serotonin, whereas in SHRs the relaxation was not affected by the contractile agonists used. The relaxation in rings contracted with KCl was abolished by Nw-nitro-l-arginine methyl ester (l-NAME) and was reduced by CPA to a similar extent in both strains. In rings contracted with serotonin, l-NAME abolished the relaxation in SHRs, but the inhibitor only partially reduced the relaxation in WKYs. CPA did not alter the relaxation in the presence of l-NAME. Endothelium-independent relaxations to sodium nitroprusside were not affected by CPA. These results suggest that acetylcholine relaxes rat femoral arteries by releasing both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF). In SHRs, the relaxation is preserved, but the release of EDHF is absent. CPA inhibits the relaxation mediated by nitric oxide, but not EDHF and, thus, inhibits the relaxation in SHRs but not in WKYs. Functional alteration of endoplasmic reticulum in the hypertensive endothelium cannot be detected.
Second Department of Internal Medicine, Nagoya City University Hospital, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Sumiyo
S
Yamashita
Koichi
K
Miyagawa
Masuo
M
Ohashi
Masaya
M
Sugiyama
Koichi
K
Sato
Ryuzo
R
Ueda
Yasuaki
Y
Dohi
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D007211:Indoles; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000109:Acetylcholine; C000543:cyclopiazonic acid