OBJECTIVE Dysfunctional cellular Ca2+ handling has been proposed to underlie the heightened vascular reactivity observed in the spontaneously hypertensive rat (SHR) model of genetic hypertension. We tested the hypothesis that basal or agonist-induced mobilization of intracellular Ca2+ is elevated in mesenteric resistance arteries of SHR compared with the normotensive Wistar-Kyoto (WKY) rat. METHODS A method using fura-2 for the simultaneous measurement of intracellular Ca2+ and isometric force generation in isolated mesenteric resistance arteries was employed to measure agonist-induced changes in Ca2+ and force during activation with 100 mmol/l K+ or 10 mumol/l norepinephrine. Arteries with normalized diameter 220-240 microns from male rats aged 14-15 weeks were examined. RESULTS No differences were detected between the rat strains in basal Ca2+ concentration or the steady-state concentration of Ca2+ achieved in response to either 100 mmol/l K+ or 10 mumol/l norepinephrine. The relationship between Ca2+ and force during the contractile responses to K+ and norepinephrine was analyzed. No differences between the strains in the level of active stress, normalized to unit intracellular Ca2+, were detected in the steady-state responses to K+ or norepinephrine. CONCLUSIONS The present results do not support the hypothesis that alterations in either the basal concentration of intracellular Ca2+ or the amount of intracellular Ca2+ mobilized in response to high levels of norepinephrine or K+ are present in resistance arteries of SHR compared with those of WKY rats. Moreover, these findings suggest that elevations in Ca2+ do not contribute to heightened peripheral resistance in SHR.