TY - JOUR T1 - INFLUENCE OF ANGIOTENSIN I, ANGIOTENSIN II AND COCAINE ON ADRENERGIC VASOCONSTRICTOR RESPONSES IN THE DOG HINDPAW JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 275 LP - 283 VL - 183 IS - 2 AU - P. J. KADOWITZ AU - C. S. SWEET AU - M. J. BRODY Y1 - 1972/11/01 UR - http://jpet.aspetjournals.org/content/183/2/275.abstract N2 - The influence of i.a. infusion of angiotensin I, angiotensin II and cocaine on vasoconstrictor responses to norepinephrine, tyramine and sympathetic nerve stimulation was evaluated in the acutely denervated and pump-perfused cutaneous vascular bed in the dog. Infusion of angiotensin I, 500 ng/min, and angiotensin II, 250 ng/min, increased systemic arterial and hindpaw perfusion pressure. Vasoconstrictor responses to sympathetic nerve stimulation were enhanced, and the shift to the left of the frequency- response curve was parallel whereas responses to norepinephrine and tyramine were not altered in the presence of both peptides. Infusion of cocaine, 50 µg/min, increased hindpaw perfusion pressure but was without effect on systemic arterial pressure. The doseresponse curve for norepinephrine and the frequency-response curve for nerve stimulation were shifted to the left in a nonparallel fashion with much greater responses obtained at the highest stimulus frequency and dose of norepinephrine while at the same time the shift to the right of the tyramine dose-response curve was parallel. Angiotensin I and angiotensin II did not modify the duration of vasoconstrictor responses to norepinephrine and nerve stimulation whereas cocaine increased the duration of responses to both exogenous and nerve-released norepinephrine. These results suggest that angiotensin I and angiotensin II in the concentration studied enhance responses to sympathetic nerve stimulation by facilitating the release of transmitter from sympathetic nerve endings and that this effect is specific for the pool of neurotransmitter released by electrical excitation of the sympathetic nerves. It is also suggested that cocaine enhances responses to norepinephrine and nerve stimulation and decreases the response to tyramine by blocking the neuronal uptake of catecholamines in the cutaneous vasculature. © 1972 by The Williams & Wilkins Co. ER -