Effect of Endothelin on Regional Hemodynamics and Renal Function in Awake Normotensive Rats

Abstract

The effects of endothelin on regional hemodynamics and renal function were studied in awake normotensive rats. Intravenous injection of endothelin (700 pmol/kg) transiently lowered mean blood pressure (from 108 .+-. 2 to 84 .+-. 2 mm Hg, p < 0.01), due to a reduction in total vascular resistance (38 .+-. 1%, p < 0.01), and increased stroke volume (29 .+-. 5%, p < 0.01) and heart rate (from 399 .+-. 18 to 447 .+-. 18 bpm, p < 0.05); mesenteric and renal blood flow was reduced (37 .+-. 13, p < 0.05 and 63 .+-. 5%, p < 0.01), whereas carotid blood flow was increased (78 .+-. 5%, p < 0.01). This effect was followed by long-lasting hypertension due to increased total vascular resistance (112 .+-. 19%, p < 0.01); stroke volume, mesenteric, and renal blood flow were reduced (34 .+-. 5, 41 .+-. 4, and 58 .+-. 4%, respectively, p < 0.05) and carotid blood flow returned to basal levels. Bilateral nephrectomy enhanced the initial hypotensive effect. Pretreatment with nifedipine blocked the hypertensive effect, whereas bilateral nephrectomy did not. A subpressor dose of endothelin (70 pmol/kg) had no effect on stroke volume, mesenteric blood flow, glomerular filtration rate, and plasma renin activity; carotid blood flow was transiently increased (48 .+-. 16%, p < 0.05), then returned to basal levels; renal blood flow decreased (22 .+-. 6 and 15 .+-. 4% at 30 s and 10 min, respectively p < 0.05). Our data show a heterogeneity in the response of regional vascular beds to endothelin, the renal and mesenteric compartments being very sensitive to its vasoconstricting action. Endothelin, acting as paracrine or endocrine hormone, might have an important role in the pathogenesis of high blood pressure.