Inhibition by nicotine of the vasodilator effect of bradykinin: evidence for a prostacyclin-dependent mechanism.

In urethane-anesthetized rabbits, bradykinin caused a dose-dependent hypotension. This hypotensive response was not altered in magnitude but was inhibited in duration after pretreatment with nicotine. Nicotine failed to inhibit the hypotensive effect of eledoisine, prostacyclin, isoprenaline and papaverine. Aspirin pretreatment, however, caused a marked inhibition in both magnitude and duration of the hypotensive effect of bradykinin without altering that of eledoisine, isoprenaline, papaverine and prostacyclin. Bradykinin also produced a concentration-dependent fall in perfusion pressure of the isolated perfused guinea-pig heart. Addition of nicotine to the perfusion medium caused a significant inhibition in both magnitude and duration of the vasodilator response to bradykinin. Nicotine did not alter the vasodilation induced by prostacyclin. Nicotine also failed to abolish the vasodilator effects of isoprenaline, histamine, papaverine and eledoisine in the coronary circulation. Other antagonists such as atropine, propranolol, cimetidine did not alter the vasodilator effect of bradykinin. These results were taken as the evidence indicating that the vasodilator action of bradykinin is mediated through the release of prostaglandins; the peptide selectivity increases the release of prostacyclin and this prostacyclin contributes to the bradykinin-induced vasodilation in guinea-pig coronary vessels.