Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats.
To study mechanisms for attenuated endothelium-dependent vasorelaxation in hypertension, we examined the effects of acetylcholine (ACh) on renal vascular resistance (RVR) and release rates of endothelium-derived relaxing factor (EDRF) in kidneys isolated from spontaneously hypertensive rats (SHR), deoxycorticosterone acetate (DOCA) salt-hypertensive (DOCA salt) rats, and Dahl salt-sensitive (Dahl S) rats. Decreases in RVR by ACh were smaller in hypertensive rats than in their normotensive controls. The release rate of nitric oxide into the perfusate, which was estimated using nitrite-nitrate as an index, did not differ between SHR and Wistar-Kyoto rats (WKY). However, the release rate of EDRF was markedly decreased in both DOCA salt rats and Dahl S rats compared with their normotensive controls (10(-7) M ACh: DOCA salt 45 +/- 6 vs. control 410 +/- 60 pmol.min-1.g-1 kidney wt, P < 0.001). In SHR, high-K+ perfusion or pretreatment with glibenclamide, inhibitors of endothelium-derived hyperpolarizing factor (EDHF), significantly reduced ACh-induced vasorelaxation only in WKY, resulting in no differences in the RVR reduction between SHR and WKY. Thus attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF, but to a decrease in EDRF in DOCA salt rats and Dahl S rats.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
H
H
Hayakawa
Y
Y
Hirata
E
E
Suzuki
T
T
Sugimoto
H
H
Matsuoka
K
K
Kikuchi
T
T
Nagano
M
M
Hirobe
T
T
Sugimoto
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003900:Desoxycorticosterone; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012079:Renal Circulation; D012965:Sodium Chloride; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D001120:Arginine; D000109:Acetylcholine; D005905:Glyburide