Comparison of the Effects of a New Vasodilator Pinacidil and Nifedipine on Isolated Blood Vessels

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Abstract
In isolated human crural veins studied in vitro, pinacidil (0.038-380 .mu.M) caused a concentration-related inhibition of 18 .mu.M noradrenaline [norepinephrine] (NA) and 127 mM K+-induced contractions. Pinacidil was more potent in inhibiting the NA-contraction than that induced by K+, whereas the reverse was seen for nifedipine. At the highest concentrations greater inhibitions of the NA-induced contractions could be obtained with pinacidil than with nifedipine. The inhibitory effect of pinacidil on the K+-induced contractions was eliminated during a 1-h wash-out period. The inhibitory effect of nifedipine could not be eliminated during 4-h repeated wash-out. Pinacidil was completely devoid of inhibitory effect on 45Ca net influx in rat aorta, whereas nifedipine caused a significant reductionof influx. Evidently, both pinacidil and nifedipine are effective vasodilators in human vessels. Pinacidil seems to be more effective in NA-induced contractions than does nifedipine. The mechanism of action of pinacidil cannot be attributed to an inhibitory effect on cellular Ca entry.