In rats with simulated peripheral artery disease, HOE-140 significantly reduced the peak mean arterial pressure response to muscle contraction (17 ± 2 vs 23 ± 2 mmHg; P=0.03).
In a rat model of simulated peripheral artery disease, bradykinin 2 receptors contribute to the exaggerated exercise pressor reflex during muscle contraction.
Absolute Event Rate: 17% vs 23%
p-value: p=0.03
We investigated the role played by bradykinin 2 (B2) receptors in the exaggerated exercise pressor reflex in rats with a femoral artery ligated for 72 h to induce simulated peripheral artery disease (PAD). We hypothesized that in decerebrate, unanesthetized rats with a ligated femoral artery, hindlimb arterial injection of HOE-140 (100 ng, B2 receptor antagonist) would reduce the pressor response to 30 s of electrically induced 1 Hz hindlimb skeletal muscle contraction, and 30 s of 1 Hz hindlimb skeletal muscle stretch (a model of mechanoreflex activation isolated from contraction-induced metabolite production). We hypothesized no effect of HOE-140 in sham-operated “freely perfused” rats. In both freely perfused ( n = 4) and “ligated” ( n = 4) rats, we first confirmed efficacious B2 receptor blockade by demonstrating that HOE-140 injection significantly reduced ( P < 0.05) the peak increase in mean arterial pressure (peak ΔMAP) in response to hindlimb arterial injection of bradykinin. In subsequent experiments, we found that HOE-140 reduced the peak ΔMAP response to muscle contraction in ligated ( n = 14; control: 23 ± 2; HOE-140: 17 ± 2 mmHg; P = 0.03) but not freely perfused rats ( n = 7; control: 17 ± 3; HOE-140: 18 ± 4 mmHg; P = 0.65). Furthermore, HOE-140 had no effect on the peak ΔMAP response to stretch in ligated rats ( n = 14; control: 37 ± 4; HOE-140: 32 ± 5 mmHg; P = 0.13) but reduced the integrated area under the blood pressure signal over the final ∼20 s of the maneuver. The data suggest that B2 receptors contribute to the exaggerated exercise pressor reflex in rats with simulated PAD, and that contribution includes a modest role in the chronic sensitization of the mechanically activated channels/afferents that underlie mechanoreflex activation.
Butenas et al. (2022) studied Simulated peripheral artery disease (PAD) (n=29). HOE-140 (B2 receptor antagonist) vs. Control was evaluated on Peak increase in mean arterial pressure (peak ΔMAP) in response to muscle contraction (p=0.03). In rats with simulated peripheral artery disease, HOE-140 significantly reduced the peak mean arterial pressure response to muscle contraction (17 ± 2 vs 23 ± 2 mmHg; P=0.03).