INFLUENCE OF COCAINE AND DESIPRAMINE ON THE CONTRACTILE RESPONSE OF ISOLATED RABBIT PULMONARY ARTERIES AND AORTAE TO TRANSMURAL STIMULATION

¹ Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto, Japan

Contractile responses of spirally cut strips of the main pulmonary artery and the thoracic aorta to transmural neural stimulation and norepinephrine were studied in relation to the presence or absence of cocaine, desipramine, pyrogallol and pheniprazine. Cocaine in concentrations of 10^-6 and 3 x 10^-6 M progressively increased the amplitude and the duration (duration at the level of the half-maximum tension) of vascular contraction induced by transmural stimulation; the prolongation of the duration exceeded greatly the tension increment. The contractile response was markedly reduced or completely abolished in vessels subjected to prolonged cold storage. Cocaine potentiated the contractile response when it was still retained but did not restore the response when abolished completely. Desipramine caused a dual effect on vascular contraction induced by transmural stimulation and norepinephrine; the contractile response was potentiated at 2 x 10^-7 M desipramine but inhibited at 10^-6 M. On the other hand, the duration of contraction was progressively prolonged with increasing concentrations of desipramine. The desipramine-induced inhibition of the contractile response to transmural stimulation was not prevented or antagonized by increasing calcium concentrations. Pyrogallol slightly potentiated the contractile response to transmural stimulation and norepinephrine, whereas pheniprazine did not affect the response. The present findings suggest that impaired utpake by cocaine of norepinephrine into nerve terminals is an important factor in potentiating the vascular response to endogenous and exogenous norepinephrine, although the possibility of supersensitivty of postsynaptic sites cannot be excluded. Further, it seems unlikely that the inhibitory effect of desipramine in rabbit aortic and arterial smooth muscles is due to its antagonism to Ca⁺⁺ responsible for muscle contractions.