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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 \u201cfreely perfused\u201d rats. In both freely perfused ( n = 4) and \u201cligated\u201d ( n = 4) rats, we first confirmed efficacious B2 receptor blockade by demonstrating that HOE-140 injection significantly reduced ( P &lt; 0.05) the peak increase in mean arterial pressure (peak \u0394MAP) in response to hindlimb arterial injection of bradykinin. In subsequent experiments, we found that HOE-140 reduced the peak \u0394MAP response to muscle contraction in ligated ( n = 14; control: 23\u2009\u00b1\u20092; HOE-140: 17\u2009\u00b1\u20092 mmHg; P = 0.03) but not freely perfused rats ( n = 7; control: 17\u2009\u00b1\u20093; HOE-140: 18\u2009\u00b1\u20094 mmHg; P = 0.65). Furthermore, HOE-140 had no effect on the peak \u0394MAP response to stretch in ligated rats ( n = 14; control: 37\u2009\u00b1\u20094; HOE-140: 32\u2009\u00b1\u20095 mmHg; P = 0.13) but reduced the integrated area under the blood pressure signal over the final \u223c20 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. <\/jats:p>","DOI":"10.1152\/ajpregu.00274.2022","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T17:31:40Z","timestamp":1671471100000},"page":"R183-R195","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Bradykinin 2 receptors contribute to the exaggerated exercise pressor reflex in a rat model of simulated peripheral artery disease"],"prefix":"10.1152","volume":"324","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2452-5018","authenticated-orcid":false,"given":"Alec L. 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