The cardiovascular and autonomic properties of N-phenylpiperazine (NPP) in several animal models.

A number of isolated tissue and intact animal models were utilized to investigate in more detail the cardiovascular actions of N-phenylpiperazine (NPP), a known compound having adrenergic blocking properties. In isolated tissues its autonomic profile is characterized by alpha and beta adrenergic blocking activity. Compared to other beta receptor antagonists, NPP displays moderate in vitro beta-1 blockade in guinea-pig atria. Cumulative administration of NPP (0.1--0.3 mg/kg i.v.) in the intact dog also produces dose-dependent inhibition of myocardial contractility following isoproterenol administration. The oral antihypertensive potency of NPP in the deoxycorticosterone acetate hypertensive rat is compared with phenoxybenzamine and labetalol. Its profile is similar to labetalol but differs from phenoxybenzamine, causing a fall in blood pressure and a decrease in heart rate. Hemodynamic data obtained with NPP in the anesthetized animal reveal a complex cardiovascular profile involving the interactions of the sympathetic nervous system. Canine hind limb perfusion studies using cumulative doses (0.1--0.3 mg/kg i.v.) appear to preclude a direct vasodilator mechanism in the reserpinized-pretreated animal. In other studies, nonselective vasoconstrictor responses induced by exogenous administration of norepinephrine and lumbar sympathetic nerve stimulation are inhibited to the same degree by NPP (0.1--10 mg/kg i.v.) autonomic interactions with NPP in the nictitating membrane provide evidence for inhibition of neuronal catecholamine uptake and catecholamine release. From the data obtained in the present study, it is suggested that NPP has a predominant influence on the response of the sympathetic nervous system to provide a unique cardiovascular profile. The manner in which blood pressure is regulated by either direct or nonselective mechanisms will be discussed.