BRADYKININ CONTRIBUTES TO THE EXERCISE PRESSOR REFLEX - MECHANISM OF ACTION

This study determined the receptors responsible for mediating bradykin in's effect on skeletal muscle afferents that cause the pressor reflex in anesthetized cats. In eight cats, 1 mug of bradykinin was injected intra-arterially into the gracilis muscle before and after intravenou s injection of a kinin B2-receptor antagonist (NPC 17731, 20 mug/kg). Initial injection of bradykinin reflexly increased mean arterial press ure 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 resp onse to bradykinin was abolished by kinin B2-receptor blockade. Simila r injection of the kinin B1-receptor agonist des-Arg9-bradykinin cause d no cardiovascular responses (n = 6). In eight different animals, mea n arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses to 30 s of electrically stimulated hind limb contraction were attenuated by 50 +/- 6, 55 +/- 7, and 41 +/- 8%, respectively, after kinin B2-receptor blockade. In eight other animal s, 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 syn thesis with indomethacin (2.5-3 mg/kg iv) and were then abolished by s ubsequent B2-receptor blockade. These data suggest that bradykinin con tributes to the exercise pressor reflex through its action on kinin B2 receptors located on the nerve endings of the muscle afferents. The m ajority of this bradykinin effect is dependent on local concentrations of prostaglandins that can augment the stimulating action of this pep tide on muscle afferent nerve endings and that may be enhanced by acti vation of kinin B2 receptors.