Effect of milrinone on contractility and 45Ca movements in the isolated rabbit aorta

The effects of milrinone on 45Ca movements and on contractile responses were studied in rabbit aortic smooth muscle. Milrinone, 10(-7)-5 x 10(-4) M, inhibited the responses induced by high K and noradrenaline (NA). These effects were observed when milrinone was added before or after the induced contractions and were similar in aortas with or without endothelium. The Ca-induced contractions of K-depolarized aortas as well as the contractions induced by caffeine in normal and in Ca-free solution were also inhibited dose dependently by milrinone. Milrinone reduced the 45Ca influx in resting or non-stimulated aortic rings as well as in aortic rings stimulated by NA. On the other hand, neither the 45Ca influx stimulated by high K or the 45Ca efflux stimulated by NA were altered by pretreatment with milrinone. It is concluded that milrinone inhibits vascular smooth muscle contractility by probably acting at multiple sites to decrease the availability of intracellular free Ca required for activation.