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THE PHARMACOLOGY OF ANTIHYPERTENSIVE DRUGS WITH SPECIAL REFERENCE TO VASODILATORS, α‐ADRENERGIC BLOCKING AGENTS AND PRAZOSIN
Author(s) -
Cambridge D.,
Davey M. J.,
Massingham R.
Publication year - 1977
Publication title -
medical journal of australia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 131
eISSN - 1326-5377
pISSN - 0025-729X
DOI - 10.5694/j.1326-5377.1977.tb107750.x
Subject(s) - prazosin , vasodilation , medicine , endocrinology , chemistry , adrenergic , pharmacology , receptor , antagonist
Prazosin causes relaxation of vascular smooth muscle and produces a non‐classical functional blockade of α‐adrenoceptors quite unlike the occupancy block caused by conventional α‐adrenoceptor blocking drugs. The antihypertensive effect of prazosin in dogs with renal hypertension is not accompanied by tachycardia or renin release and the development of tolerance is not a problem. It has been shown by measuring impulse traffic in the carotid sinus nerve in cats that prazosin considerably increases baroreceptor sensitivity, presumably as a consequence of smooth muscle relaxation and enhanced distensibility in the carotid sinus region. This probably contributes to the overall antihypertensive response. The recent realization, principally through the work of Langer et alii , Starke and Rand et alii of the existence of an important local control mechanism at the terminal ramifications of adrenergic nerves in which noradrenaline regulates its own release through a negative feedback mechanism, mediated by prejunctional α‐receptors, prompted the determination of prazosin's affinity for the latter sites. Prazosin was found to be completely devoid of affinity for prejunctional α‐receptors, which not only explains the absence of tachycardia and renin release after prazosin administration, but affords support to the important suggestion of Rand et alii as to why the original clinical expectations of α‐adrenoreceptor antagonists in hypertension were not fulfilled. This was hypothesized as due to the loss of the feedback inhibitory loop and consequent enhancement of release of noradrenergic transmitter that resulted from their blocking prejunctional in addition to postjunctional α‐adrenoceptors. In preliminary experiments employing 2‐ 14 C‐prazosin, inconclusive evidence was obtained of the release of prazosin from neuronal storage sites in response to nerve stimulation.