Differential effects of vasopressin and endothelin-1 on vascular contractile and calcium responses in pressurized small arteries from spontaneously hypertensive rats

OBJECTIVE: To investigate the effects of vasopressin and endothelin-1 on the intracellular free calcium concentration ([Ca2+]i) and on contractile responses in endothelium-denuded resistance vessels of prehypertensive (5-week-old) and adult hypertensive (17-week-old) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats. METHODS: Segments (2 mm long) of third-order branches of small mesenteric arteries were mounted in a perfusion myograph and maintained at 60 mmHg pressure. Endothelium was removed by intraluminal passage of air. The vessel [Ca2+]i was measured by fura-2 fluorescence and contraction was determined using a video imaging system to record lumen diameter. RESULTS: Lumen diameter was significantly smaller in 5-and 17-week-old SHR than it was in age-matched WKY rats (5 week-old SHR versus WKY rats: 178 +/- 4.0 versus 195 +/- 4.3 microns; 17-week-old SHR versus WKY rats: 168 +/- 7.0 versus 230 +/- 3.1 microns). The basal [Ca2+]i was significantly higher in 5- and 17-week-old SHR than it was in age-matched WKY rats. Infusions of vasopressin and endothelin-1 increased [Ca2+]i and contractile responses in a dose-dependent manner in all groups. The vasopressin-induced change in [Ca2+]i was significantly greater in 5- and 17-week-old SHR than in age-matched controls. The sensitivity of [Ca2+]i to vasopressin was increased in adult SHR compared with WKY rats (pD2 9.0 +/- 0.1 in SHR, 8.2 +/- 0.3 in WKY rats). Vasopressin-stimulated contractile responses were increased in adult SHR. The endothelin-1-induced change in [Ca2+]i did not differ between WKY rats and SHR. The contractility of vessels in response to endothelin-1 infusion was similar in age-matched groups. CONCLUSIONS: Endothelin-1-induced changes in [Ca2+]i and contractile responses in small arteries are similar in age-matched WKY rats and SHR, whereas responses to vasopressin are significantly enhanced in SHR compared with WKY rats. Thus [Ca2+]i signalling for vasopressin is more active than is that for endothelin-1. Vasopressin but not endothelin-1 might play a role in the development of hypertension in SHR.