Endogenous bradykinin in the thoracic spinal cord contributes to the exercise pressor reflex.
This investigation tested the hypothesis that bradykinin causes excitatory effects in the thoracic spinal cord that augment the exercise pressor reflex. Thus we performed 30 s of electrically stimulated static contraction of the hindlimb in the anesthetized cat (alpha-chloralose) to provoke reflex-induced increases in mean arterial pressure, maximal rate of rise of left ventricular pressure (dP/dt), and heart rate (i.e., the exercise pressor reflex). These three responses were compared before and 15 min after intrathecal injection of 2 micrograms (n = 3), 10 micrograms (n = 6), or 50 micrograms (n = 3) of the selective bradykinin B2- receptor antagonist HOE-140 into the thoracic spinal cord or 10 micrograms of this antagonist into the lumbar (n = 3) spinal cord. In three of the six cats in which 10 micrograms of HOE-140 were injected into the thoracic spinal cord, an additional contraction was performed 60-90 min after treatment. The 2-microgram dose of HOE-140 had no effect on the exercise pressor reflex. Injection of 10 micrograms of this antagonist into the thoracic spinal cord reduced the contraction-evoked pressor, maximal dP/dt, and heart rate responses by 49 +/-7, 58 +/- 4, and 64 +/- 13%, respectively (P < 0.05). Fifty micrograms of HOE-140 failed to attenuate these responses further. In the three cats in which an additional contraction was performed 60-90 min after treatment with 10 micrograms of the antagonist, blood pressure and dP/dt responses had returned, in part, toward initial values. Neither intravenous (n = 3) nor intrathecal injection of 10 micrograms of HOE-140 into the lumbar spinal cord had any effect on the contraction-induced cardiovascular responses. Thoracic injection of 50-200 ng of bradykinin provoked a pressor response of 26 +/- 5 mmHg that was abolished by a similar injection of 10 micrograms of HOE-140. These data suggest that endogenous bradykinin contributes to the exercise pressor reflex by an excitatory action in the thoracic spinal cord.
Department of Internal Medicine, University of California, Davis 95616, USA.
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D013904:Thoracic Vertebrae / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C065679:icatibant; D001920:Bradykinin