Bradykinin B 2-receptors mediate the pressor and renal hemodynamic effects of intravenous bradykinin in conscious rats

Abstract

Bradykinin (BK) is a peptide which evokes remarkably different changes in cardiovascular function. Systemic bolus injection of BK results in a rapid drop in blood pressure via an endothelium-dependent mechanism. On the other hand, local administration of BK can activate a powerful pressor reflex by stimulating afferent nerves located in the abdominal viscera, the heart, and the kidney. In the present study, the cardiovascular and renal hemodynamic effects during sustained (intravenous infusion) and transient (intravenous bolus injection) elevations in circulating BK were characterized and the receptor mechanism eliciting these effects was investigated. Mean arterial pressure (MAP), heart rate (HR), and renal blood flow (RBF) were recorded from conscious unrestrained rats while five-point cumulative dose-response curves were constructed during infusion or bolus injection of BK (5–80 μg kg −1). Infusion of BK produced dose-dependent increases in MAP (maximum response=27±3 mm Hg) accompanied by a significant tachycardia (maximum response=159±20 bpm), a 28±6% increase in RBF, and no changes in renal vascular resistance (RVR). The BK-induced increases in MAP, HR, and RBF were abolished after treatment with a ganglion blocker (maximum responses: MAP=2±3 mm Hg, HR=13±4 bpm, RBF=4±2%) or with an agent which blocks B 2-receptors (maximum responses: MAP=1±1 mm Hg, HR=6±5 bpm, RBF=6±2%). In marked contrast, bolus administration of BK resulted in hypotensive responses (maximum decline in MAP=−37±4 mm Hg), reflex tachycardia (maximum increase in HR=45±9 bpm), increases in RBF (maximum response=13±4%), and significant reductions in RVR (maximum response=38±5%). These responses were also prevented when B 2-receptors were blocked (maximum responses: MAP=3±2 mm Hg, HR=17±6 bpm, RBF=3±3%, RVR=9±4%). In summary, BK infusions activated a cardiopressor reflex while BK injections caused hypotension. These opposite effects were both mediated via B 2-receptors. These findings suggest that BK can have complex effects on the cardiovascular system that may be dependent on the sites, magnitude, and duration of elevated BK concentrations.