In vitro vascular reactivity to endothelin: a comparison between young and old normotensive and hypertensive rats

In this study we have investigated whether the vascular smooth muscle of a large capacitance artery of spontaneously hypertensive rats (SHR) is hyperresponsive to endothelin-1 and whether the arterial responsiveness to endothelin-1 is affected by aging. Isometric contractions of spirally cut aortic strips from SHR of 11, 22, 33 and 44 weeks of age and from age-matched WKY were measured in parallel. The vessels from SHR did not exhibit a greater responsiveness to endothelin-1 than those from WKY. No difference of responsiveness to the peptide was found among the arteries isolated from WKY of different ages. In contrast, a progressive decrease of responsiveness to endothelin-1 with aging was observed in SHR. This finding seems to be specific for endothelin-1, since the responsiveness to norepinephrine was unchanged. The significant decrease of aortic responsiveness in SHR with aging might be due to chronic hypertension and indicate desensitization to endothelin-1. The latter might be related to chronic in vivo hyperproduction of endothelin, either genetically determined or related to the hypertension-induced endothelial damage.