Effect of Endothelin on regional hemodynamics and renal function in awake normatensive rats.

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 less than 0.01), due to a reduction in total vascular resistance (38 +/- 1%, p less than 0.01), and increased stroke volume (29 +/- 5%, p less than 0.01) and heart rate (from 399 +/- 18 to 447 +/- 18 bpm, p less than 0.05); mesenteric and renal blood flow was reduced (37 +/- 13, p less than 0.05 and 63 +/- 5%, p less than 0.01), whereas carotid blood flow was increased (78 +/- 5%, p less than 0.01). This effect was followed by long-lasting hypertension due to increased total vascular resistance (112 +/- 19%, p less than 0.01); stroke volume, mesenteric, and renal blood flow were reduced (34 +/- 5, 41 +/- 4, and 58 +/- 4%, respectively, p less than 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 less than 0.05), then returned to basal levels; renal blood flow decreased (22 +/- 6 and 15 +/- 4% at 30 s and 10 min, respectively p less than 0.05).