INTERACTIONS BETWEEN HYDRALAZINE, PROPILDAZINE AND PURINES ON ARTERIAL SMOOTH MUSCLE

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Abstract
1 The interaction of hydralazine (Hyd) and propildazine (Pyd) with purine compounds was studied in the isolated tail artery from normotensive Wistar (NW) rats. 2 Exogenously added purines inhibit non competitively the antispasmogenic response to Hyd in denervated NW segments. The order of potency is 2-Cl-adenosine > adenosine > adenosine 5′-triphosphate (ATP)> inosine. Pyd action is modified only by the most active purine 2-C1-> adenosine, which displaces the dose-response curves to the right. Hyd and Pyd seem to act on the same site, since their maximal effects are not additive. 3 Theophylline (Theo) 50μm induces the appearance of the antispasmogenic effect of Hyd in the usually poorly responsive innervated proximal NW arterial segments. The potentiating action of Theo is identical to the enhancement of the Hyd response observed after 6-hydroxydopamine denervation. This result suggests that the release of endogenous purines from sympathetic nerves is sufficient to block the smooth muscle responses to Hyd, under our experimental conditions. A similar potentiating effect is obtained with propranolol (5 μm). 4 The spontaneous release of 3H, after loading with [3H]-noradrenaline, was considered as an indirect indication of purine leakage from nerve terminals. There is an inverse relationship between the rate of 3H release, under these conditions, and the magnitude of the relaxant response to Hyd, i.e., 3H leakage is higher in proximal NW segments. 5 The most satisfactory explanation for the interaction of Hyd and Pyd with exogenous purines, and for the modulating actions of sympathetic nerve terminals, is that both antihypertensives act on a common receptor, sensitive to endogenous ATP and adenosine.