Cardiovascular reflexes arising from the gallbladder of the cat. Effects of capsaicin, bradykinin, and distension.

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Abstract
We have studied the cardiovascular responses which can be evoked when the gallbladder is stimulated pharmacologically or mechanically. To determine the potential for reflex cardiovascular activation, we applied capsaicin, a selective thin-fiber agonist, to the serosal surface of the gallbladder. This algesic substance evoked cardiovascular responses which included increases in mean arterial pressure (MAP) by 14%, heart rate (HR) by 3%, left ventricular dP/dt at 40 mm Hg developed pressure (dP/dt DP40) by 14%, and systemic vascular resistance (SVR) by 19%. There were no demonstrable effects on the cardiovascular system when this same substance was applied to the surface of the liver. Bilateral vagotomy at the level of the diaphragm did not alter the responses to capsaicin. Right atrial overdrive pacing did not reduce the positive inotropic effect elicited when the gallbladder was stimulated. Removal of the celiac and superior mesenteric ganglia, or selective denervation of the gallbladder, abolished the cardiovascular responses which were evoked previously. beta-Adrenergic blockade, however, abolished only the reflex chronotropic and intropic responses. Thus, the potential for eliciting reflex cardiovascular alterations by stimulating gallbladder afferents with capsaicin was established. In subsequent studies, stimulating the gallbladder with bradykinin, an endogenous polypeptide, evoked a reflex activation of the cardiovascular system similar to that seen with capsaicin (MAP = 14%; HR = 4%; dP/dt DP40 = 18%; SVR = 14%). These reflex responses were dose dependent, were produced by mucosal as well as serosal application of this substance, and were eliminated by bilateral splanchnic nerve action. In contrast to capsaicin and bradykinin, distension of the gallbladder did not cause any cardiovascular alterations. We conclude that stimulation of gallbladder afferents by the algesic substance capsaicin or by bradykinin, an endogenous substance that under certain conditions may be formed in bile, can induce significant reflex activation of the cardiovascular system.