Dissociation of coronary artery contractile hyperreactivity from hypertension

Abstract

Background Both coronary artery contractile hyperreactivity and hypertension are associated with increased coronary artery disease. It is not known how coronary artery contractile hyperreactivity relates to hypertension. The current study tests the hypothesis that coronary artery contractile hyperreactivity can be dissociated from hypertension and therefore may contribute to the etiology of CAD independent of hypertension. Methods The contractile responses to 5-hydroxytryptamine (5-HT) and guanosine triphosphate (GTP) were determined in intact (nonpermeabilized) and α-toxin–permeabilized coronary artery strips and small mesenteric artery strips isolated from four rat strains: spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), WKY-derived hypertensive rats (WKHT), and WKY-derived hyperactive rats (WKHA). Results The SHR and WKHT were hypertensive, whereas the WKY and WKHA subjects were normotensive. The coronary artery contractile reactivity to 5-HT was significantly higher in SHR when compared with WKY. The coronary artery contractile reactivity was of similar magnitude in WKHA and WKHT and was intermediate between that of SHR and WKY rats. GTP-induced Ca 2+ sensitization of contractions were significantly greater in SHR than in WKHT, WKHA, and WKY; in comparison, no significant difference was found among WKHT, WKHA, and WKY. In contrast to the findings in coronary arteries, there was no significant difference in 5-HT–induced contractions in small mesenteric artery strips isolated from SHR and WKY. Conclusions Coronary artery contractile reactivity to 5-HT does not correlate entirely with blood pressure (BP) values. In addition, G-protein–mediated Ca 2+ sensitization of contraction was increased and contributed to the coronary artery contractile hyperreactivity in SHR.