Cardiovascular responses to milrinone in pertussis toxin-pretreated pithed rats

The modulating effects of pertussis toxin on angiotensin II and B-HT 920-evoked hemodynamic changes were compared with those of milrinone to evaluate the possible role of guanine nucleotide regulatory proteins (G proteins) in the mechanism of action of milrinone. Both milrinone and pertussis toxin shifted the blood pressure dose-response curves of B-HT 920 to the right, but the responses to angiotensin II were decreased after milrinone pretreatment only. The increase in cardiac frequency evoked by milrinone and isobutylmethylxanthine (IBMX) was not sensitive to pertussis toxin. In contrast, the decrease in systolic blood pressure elicited by milrinone could be prevented by pertussis toxin pretreatment, suggesting the involvement of a regulatory protein. Milrinone and IBMX did not influence the effects of arecoline on blood pressure or heart rate in either normal or pertussis toxin-pretreated rats. It is concluded that milrinone may affect a G protein, but not the adenylate cyclase-associated inhibitory protein, Gi.