Effects of bradykinin and icatibant on renal hemodynamics in conscious spontaneously hypertensive and normotensive rats.

We investigated the effects of bradykinin (BK) and icatibant (HOE 140), a highly selective bradykinin-B2-receptor antagonist, on mean arterial blood pressure (MAP), heart rate (HR), renal blood flow (RBF), and renal vascular resistance (RVR) in conscious Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Experiments were performed in conscious male WKY rats and SHRs instrumented over the long term with arterial and venous catheters and a transit-time flow probe for measurement of RBF. In WKY rats (n = 16), intraaortic (i.a.) bolus injections of BK (0.1, 1.0, and 10 microg) produced dose-dependent decreases in MAP and RBF with reciprocal increases in RVR. Intrarenal (i.r.) injections of BK (10 microg; n = 6) induced the same hemodynamic response pattern, although the increase in RVR was higher compared with i.a. injections (p < 0.05). Neither vasopressin V1-receptor nor alpha1-adrenoceptor blockade had an effect on the renal vasoconstrictor responses on i.a. BK. The i.a. injections of icatibant (0.1, 1.0, 5.0, and 10 microg; n = 6-10 for each dose) led to a dose-dependent blockade of the hemodynamic responses to BK (10 microg, i.a.). Icatibant (10 microg, i.a) had no effect on resting MAP and HR but induced a biphasic response in RBF and RVR with significant changes compared with basal values (p < 0.05). In SHRs (n = 9), after injection of increasing i.a. doses of BK (0.1, 1.0, and 10 microg), dose-dependent decreases in MAP were proportionately greater compared with those in WKY rats. In contrast to WKY rats, RBF and RVR exhibited a biphasic response pattern on BK in SHRs. Neither vasopressin V1-receptor nor alpha1-adrenoceptor blockade had an effect on the renal vasoconstrictor responses on i.a. BK. The i.a. injections of icatibant (10 microg) almost completely blocked the hemodynamic responses on BK in SHRs (n = 13). Icatibant (10 microg, i.a.) itself induced an increase in resting MAP and HR (p < 0.05) and a biphasic response in RBF and RVR with significant changes of basal values (p < 0.05). Our results provide evidence that BK exhibits renal vasoconstrictor and vasodilator properties in vivo, both mediated by B2-receptors. Furthermore, we demonstrated that SHRs display an increased B2-receptor-mediated vasodilatory responsiveness to BK. Finally we showed that blockade of B2 receptors leads to an increase of MAP in SHRs in contrast to WKY rats, suggesting an important role of the kallikrein/kinin system in the regulation of high blood pressure in SHRs.