Ca2+ and contractile responses of resistance vessels of WKY rats and SHR to endothelin-1.

Endothelin-1 (ET-1) influences vascular function by modulating intracellular free Ca2+ concentration ([Ca2+]i) in smooth muscle. This study investigated the effects of ET-1 on [Ca2+]i and contractile responses in resistance vessels of young prehypertensive (5 week) and adult hypertensive (17 week) spontaneously hypertensive rats (SHRs) and in age-matched normotensive Wistar-Kyoto (WKY) rats. Third-order branches of mesenteric arteries were mounted in a perfusion myograph and maintained at 60 mm Hg. Vessel [Ca2+]i was measured by Fura-2 and contraction was determined using video imaging to record lumen diameter. [Ca2+]i was higher (p < 0.01) in 5- and 17-week SHRs compared with 5- and 17-week WKYs rats. ET-1 increased [Ca2+]i and contractile responses in a dose-dependent manner in all groups. ET-induced [Ca2+]i change and vessel contractility were not significantly different between age-matched SHR and WKY groups, but [Ca2+]i responses were more sensitive in 5- compared with 17-week SHRs. These data demonstrate that ET-1-stimulated [Ca2+]i and contractile responses in resistance arteries are similar in age-matched WKY rats and SHRs and are blunted in adult SHRs compared with young prehypertensive rats. Therefore, ET-1 may not play a major role in the development of hypertension in SHRs.