Differences in regional vascular sensitivity to endothelin-1 between spontaneously hypertensive and normotensive...

1. The systemic and regional haemodynamic effects of porcine endothelin-1 (endothelin) have been measured in anaesthetized spontaneously hypertensive (SH) rats rendered areflexic by ganglion blockade; comparisons were made with age-matched Wistar-Kyoto (WKY) control animals. 2. In both SH and WKY rats endothelin (0.1-1 nmol kg-1 i.v.) elicited an initial, short-lived (less than 2 min), fall in blood pressure which was associated with substantial increases in hindquarter and carotid vascular conductances. Both the blood pressure falls and the peripheral vasodilator responses were greater in SH than in WKY rats. 3. The initial depressor effects of endothelin were followed by marked and sustained increases in blood pressure associated with constriction in carotid, hindquarter, renal and mesenteric vascular beds. Vasoconstrictor responses were quantitatively similar in the two rat strains. 4. Pretreatment with indomethacin (5 mg kg-1 i.p. or i.v.) did not alter the responses to endothelin, 1 nmol kg-1, in SH rats. 5. The regional haemodynamic effects of intravenously administered acetylcholine (0.01-1 microgram kg-1), nitroprusside (0.3-10 micrograms kg-1) and angiotensin II (0.01-0.1 microgram kg-1) were similar in SH and WKY rats. 6. Endothelin (10(-10)-3 x 10(-8) M) contracted aortic rings from both SH rats and WKY control animals. Removal of the endothelium enhanced significantly the sensitivity of tissues from both WKY and SH rats to endothelin; the increase in sensitivity was greater in tissues from SH than WKY rats. 7. The results demonstrate qualitative similarities in the complex haemodynamic effects of endothelin in SH rats and WKY control animals. However, the SH rats display substantially greater vasodilator responses to endothelin than WKY. Eicosanoid generation is not the mechanism of the vasodilator action of endothelin in SH rats under the conditions of our experiments.