Endothelium-derived relaxing factor responses in Doca-salt hypertensive rats.
This study examined the contribution of endothelium-derived relaxing factor (EDRF) to the susceptibility of uninephrectomized rats to deoxycorticosterone acetate (DOCA)-salt hypertension. N omega-nitro-L-arginine, a probe for EDRF, produced smaller increases (P < 0.001) in mean arterial pressures in anesthetized hypertensive DOCA-salt rats than in sham rats. Acute L-arginine administration (300 mg/kg body wt i.v.) failed to reduce pressure in anesthetized DOCA-salt rats. Chronic oral and intraperitoneal L-arginine did not lower pressure in conscious DOCA-salt rats with established hypertension, nor did it prevent hypertension when begun in prehypertensive DOCA-salt rats. Preconstricted aortic rings from DOCA-salt rats had attenuated relaxation to acetylcholine compared with sham rats. Rings L-arginine-treated DOCA-salt rats had responses similar to DOCA-salt rats. Relaxation to nitroprusside was not different between any rat group. Thus EDRF is attenuated in DOCA-salt hypertension. However, unlike several other hypertensive models, the blunted EDRF response cannot be overcome by provision of L-arginine. These data suggest synthesis or release of EDRF may be noncompetitively inhibited in DOCA-salt hypertension.
Kirchner
K A
KA
Department of Medicine, University of Mississippi Medical Center, Jackson 39216-4505.
Scanlon
P H
PH
Dzielak
D J
DJ
Hester
R L
RL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D013997:Time Factors; D014664:Vasodilation
D019335:Nitroarginine; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D001120:Arginine; D000109:Acetylcholine