Differences in regional vascular sensitivity to endothelin‐1 between spontaneously hypertensive and normotensive Wistar‐Kyoto rats

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Abstract
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 (−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 μg kg−1), nitroprusside (0.3–10 μg kg−1) and angiotensin II (0.01–0.1 μg kg−l) were similar in SH and WKY rats. 6 Endothelin (10−10−3 × 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.