This study was conducted to determine if increased vascular contractile sensitivity to serotonin in spontaneously hypertensive (SHR) rats is linked with increased phosphoinositide turnover. Aortic and mesenteric artery rings from SHR exhibited 6.2- and 5.0-fold greater contractile sensitivity to serotonin than the aortic and mesenteric artery rings from normotensive Wistar-Kyoto (WKY) rats. Serotonin-induced turnover of phosphoinositide was measured by quantifying the accumulation of [3H] inositol labeled inositol monophosphate (IP), inositol bisphosphate (IP2) and inositol trisphosphate (IP3). Serotonin (3, 30, 200 microM) induced significantly greater accumulation of IP in SHR (279%, 590%, 895%) than in WKY (24%, 127%, 328%) aortic rings. Similarly, 3, 30 and 200 microM serotonin induced significantly greater accumulation of IP2 (118%, 241%, 451%) and IP3 (90%, 100%, 247%) in SHR than the accumulation of IP2 (15%, 58%, 122%) and IP3 (19%, 27%, 73%) in WKY aortic rings. Based on these data it is suggested that the greater vascular sensitivity to serotonin in SHR, at least in part, is attributable to increased turnover of phosphoinositide.