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1 The characteristics of semicarbazide-sensitive amine oxidase (SSAO) are reviewed and the unknown physiological or pathological role of this enzyme emphasized. 2 The various mechanisms of action proposed for the vasodilator drug hydralazine are considered. In particular, the inhibitory action on various enzymes, related or not to cardiovascular function, are discussed. 3 Studies linking inhibition of SSAO to hydralazine hypotension are reviewed and a general hypothesis relating both actions is presented. The hypothesis postulates that (a) vascular SSAO is involved in the regulation of vascular tone, and (b) hydralazine vasodilation is the consequence of vascular SSAO inhibition. 4 Evidence supporting these postulates is presented and vascular SSAO inhibition is proposed as a novel mechanism of vasodilation. [ABSTRACT FROM AUTHOR]

Summary 1 It is generally recognized that the vasodilator hydralazine produces hypotension accompanied by baroreflex-mediated tachycardia. In some experimental conditions, however, the accompanying heart rate change is bradycardia, a paradoxical response which has not been satisfactorily explained. The present study examined the possibility of hydralazine-induced bradycardia being mediated by vagal or sympathetic afferents activated by changes in left ventricular pressure. 2 Systolic blood pressure and heart rate responses to hydralazine were recorded in conscious normotensive intact rats by a tail cuff method and compared with responses in animals subjected to previous sino-aortic deafferentation (SAD) to remove the influence of the arterial baroreflex. Responses were also obtained after blockade of myocardial afferent vagal C-fibres with urethane, of efferent vagal impulses to the heart with methylatropine, of positive inotropic effects of hydralazine with atenolol, and of prostanoid sensitization of myocardial nerve fibres with indomethacin. 3 Hydralazine produced hypotension and tachycardia in intact rats, and hypotension and bradycardia in SAD animals. In intact rats, this pattern was not affected by any of the pretreatments, while in SAD rats, all pretreatments reversed the bradycardia to hydralazine. 4 The present results indicate that suppression of the arterial baroreflex by SAD propitiates the appearance of a bradycardiac response to hydralazine. This reaction probably results from activation of a vagal cardiodepressant reflex originating in the heart, as suggested by its blockade by drugs acting at various sites along the reflex arch. [ABSTRACT FROM AUTHOR]