Blood pressure responses to hindlimb arterial bradykinin injection are mediated by bradykinin 2 receptors in decerebrate rats

Abstract

Mechanical and metabolic signals associated with skeletal muscle contraction activate a reflex that increases blood pressure during exercise (i.e., the exercise pressor reflex). Bradykinin is one metabolite that has been found to play a role in activating the exercise pressor reflex and also contribute to the reflex's exaggeration in a rat model of simulated peripheral artery disease (PAD) induced by chronic femoral artery ligation. Specifically, bradykinin 2 (B2) receptor expression was found to be greater in rat dorsal root ganglia (DRG) tissue of “ligated” rats compared to the expression found in DRG tissue of rats in which the femoral artery was patent (i.e., “freely perfused”). Moreover, the hindlimb arterial injection of bradykinin reflexly increased blood pressure more in ligated rats than it did in freely perfused rats. We tested the hypotheses that, 1) HOE‐140 (5 μg/kg), a selective B2 receptor antagonist, would reduce the pressor response to bradykinin (0.5 μg/kg) injection in both ligated and freely perfused decerebrate, unanesthetized rats and 2) the magnitude of the reduction would be greater in ligated rats than in freely perfused rats. In five rats in which a femoral artery was ligated 72 hours before the experiment, HOE‐140 significantly reduced the pressor response to bradykinin injection (control: 23±2, post HOE‐140: 5±1 mmHg; p<0.01). In freely perfused rats, bradykinin injection evoked pressor responses in two rats and depressor responses in four rats. HOE‐140 reduced the magnitude of the pressor response (control: 16±7, HOE‐140: 4±2 mmHg, n=2) and the depressor response (pre: −22±5, post: −2±1 mmHg; p=0.02, n=4) in those experiments. We hypothesized that the depressor response in the freely perfused rats was due to the fact that hindlimb blood flow was not arrested during bradykinin injection and, therefore, the vasodilatory effects of bradykinin overwhelmed reflex‐mediated vasoconstriction. In four additional freely perfused rats in which a depressor response to bradykinin injection was initially observed (−31±8 mmHg), we subsequently tightened an iliac artery/vein snare to arrest the hindlimb circulation. Tightening the snare in this manner unmasked bradykinin injection‐induced pressor responses (9±4 mmHg). We conclude that hindlimb arterial bradykinin injection in ligated rats consistently produced a pressor response that was mediated by B2 receptors. In freely perfused rats, the divergent responses to bradykinin injection (i.e., pressor or depressor) were also B2 receptor mediated. B2 receptors may play a role in evoking the exaggerated exercise pressor reflex that is found in the rat model of simulated PAD.Support or Funding InformationSupported by University/Department funds.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.