Comparison of the effects of a new vasodilator pinacidil and nifedipine on isolated blood vessels.
In isolated human crural veins studied in vitro pinacidil (0.038-380 microM) caused a concentration-related inhibition of noradrenaline, 18 microM (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 hr wash-out period. In contrast to this, the inhibitory effect of nifedipine could not be eliminated during 4 hrs repeated wash-out. Pinacidil was completely devoid of inhibitory effect on 45Ca net influx in rat aorta, whereas nifedipine caused a significant reduction of influx. The results indicate that both pinacidil and nifedipine are effective vasodilatators 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 calcium entry.
D000328:Adult; D001013:Aorta, Thoracic / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002132:Calcium Radioisotopes; D006146:Guanidines; D011725:Pyridines; D014665:Vasodilator Agents; D020110:Pinacidil; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine