[Role of superoxide anion on onset and maintenance of hypertension in spontaneously hypertensive rats].
Endothelium-derived relaxing factor (EDRF) is a substance that is released by the vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine (AC). Superoxide anion (O2-) inactivates EDRF. It is well known that the endothelium-dependent vascular relaxations to AC are depressed in the aorta of spontaneously hypertensive rats (SHR). We studied the role of O2- on onset and maintenance of hypertension in SHR. Male 4- and 17-week old SHR (4SHR, 17SHR), and enalapril treated 17-week old SHR (5 mg/kg/day for 4 weeks: ETSHR), and age-matched normotensive Wistar-Kyoto rats (WKY; 4WKY, 17WKY) were used. Relaxation responses to AC or superoxide dismutase (SOD) were measured in isolated aortae from rats. Mean arterial pressure (MAP) was measured after injection of SOD in rats under conscious state. Systolic blood pressure of 4SHR, 17SHR, ETSHR, 4WKY, and 17WKY were 129 +/- 2 mmHg, 203 +/- 3 mmHg, 158 +/- 3 mmHg, 97 +/- 1 mmHg, and 138 +/- 2 mmHg, respectively. Although relaxation responses to AC were decreased in aortae from 4SHR, 17SHR, and ETSHR compared with those from age-matched WKY, relaxation responses to SOD dit not differ between SHR and corresponding WKY. Whereas the injection of SOD(10000 U/kg) elicited a significant reduction of MAP in 4SHR (-11 +/- 3 mmHg) and 17SHR (-24 +/- 5 mmHg), it has no effect in WKY. These data suggest that AC mediated endothelium-dependent relaxation is attenuated in SHR and that excessive O2- in the endothelium resulted from hypertension may contributes the decreased response in SHR.
Yamamoto
N
N
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Otsuka
Y
Y
Kushiro
T
T
Kajiwara
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000838:Anions; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000209:etiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D000838:Anions; D013481:Superoxides; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D000109:Acetylcholine