Bradykinin contributes to the exercise pressor reflex: mechanism of action.
This study determined the receptors responsible for mediating bradykinin's effect on skeletal muscle afferents that cause the pressor reflex in anesthetized cats. In eight cats, 1 microgram of bradykinin was injected intra-arterially into the gracilis muscle before and after intravenous injection of a kinin B2-receptor antagonist (NPC 17731, 20 micrograms/kg). Initial injection of bradykinin reflexly increased mean arterial pressure by 23 +/- 7 mmHg, maximal change in pressure over time by 439 +/- 272 mmHg/s, and heart rate by 11 +/- 4 beats/min. The hemodynamic response to bradykinin was abolished by kinin B2-receptor blockade. Similar injection of the kinin B1-receptor agonist des-Arg9-bradykinin caused no cardiovascular responses (n = 6). In eight different animals, mean arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses to 30 s of electrically stimulated hindlimb contraction were attenuated by 50 +/- 6, 55 +/- 7, and 41 +/- 8%, respectively, after kinin B2-receptor blockade. In eight other animals, mean arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses were reduced by 58 +/- 8, 66 +/- 6, and 40 +/- 12%, respectively, after inhibition of prostaglandin synthesis with indomethacin (2.5-3 mg/kg iv) and were then abolished by subsequent B2-receptor blockade. These data suggest that bradykinin contributes to the exercise pressor reflex through its action on kinin B2 receptors located on the nerve endings of the muscle afferents.(ABSTRACT TRUNCATED AT 250 WORDS)
Pan
H L
HL
Department of Internal Medicine, University of California, Davis 95616.
Stebbins
C L
CL
Longhurst
J C
JC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D002415:Cats; D005260:Female; D006614:Hindlimb / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology*; D011448:Prostaglandin Antagonists; D018002:Receptors, Bradykinin / Q000187:drug effects; D012018:Reflex / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065168:Bradykinin Receptor Antagonists; D009842:Oligopeptides; D011448:Prostaglandin Antagonists; D018002:Receptors, Bradykinin; C071327:NPC 17731; C024626:bradykinin, des-Arg(9)-; C065679:icatibant; D001920:Bradykinin; D007213:Indomethacin