Hemodynamic characterization of pinacidil in rats. Comparison with hydralazine.

Pinacidil (N"-cyano-N-4-pyridyl-N'-1,2,2-trimethylpropylguanidine monohydrate; P1134) is a new vasodilator drug with a direct relaxant effect on vascular smooth muscle. Its hemodynamic properties, in comparison with those of hydralazine, were studied in conscious normotensive and spontaneously hypertensive rats; anesthetized normotensive rats; pithed normotensive rats; pithed normotensive rats subjected to electrical stimulation of the spinal cord. Radioligand binding studies on rat cerebral membranes were carried out to study a possible affinity for pinacidil towards alpha 1- and alpha 2-adrenoceptors, respectively. The observations made in conscious and anesthetized rats suggest that both pinacidil and hydralazine are predominantly arterial vasodilators. In conscious animals reflex tachycardia was elicited by both drugs. Neither pinacidil nor hydralazine possessed substantial affinity for alpha 1- or alpha 2-adrenoceptors, as concluded from radioligand binding studies. Pinacidil interferes with the pressor response to postsynaptic alpha 2-adrenoceptor stimulation in pithed rats, possibly reflecting weak calcium antagonistic activity of the drug. Pinacidil did not interfere with the electrically induced release of noradrenaline from presynaptic sites. All results suggest that pinacidil is a direct-acting arteriolar dilator, which on a molar base is somewhat more potent than hydralazine.