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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]

The effects of intracoronary administration of histamine on atrial and ventricular contractility were determined in a paced canine isovolumic heart preparation. Contractility was assessed by recording the pressure developed in saline-filled balloons placed in each of the four cardiac chambers. At doses above 0.1 mg and up to 100 mg histamine produced dose-related positive inotropic responses in all chambers. These were preceded by transient negative effects. The positive responses were not affected by a combination of H and H receptor antagonists antazoline and cimetidine but were almost completely abolished by the beta adrenoceptor, blocker timolol. The negative responses were uninfluenced by either treatment. It was concluded that, in the canine isovolumic heart not subjected to complicating chronotropic and extracardiac factors, moderate doses of histamine are devoid of inotropic effects. Higher doses do produce myocardial stimulation, not mediated by histamine receptors, but probably due to norepinephrine release. These responses are preceded by transient non-specific depressant effects. [ABSTRACT FROM AUTHOR]

Summary High doses of isoniazid increase hypotension induced by vasodilators and change the accompanying reflex tachycardia to bradycardia, an interaction attributed to decreased synthesis of brain γ-aminobutyric acid (GABA). In the present study, the possible enhancement by isoniazid of bradycardia induced by β-adrenoceptor antagonists was determined in rats anaesthetised with chloralose-urethane. Isoniazid significantly increased bradycardia after propranolol, pindolol, labetalol and atenolol, as well as after clonidine, but not after hexamethonium or carbachol. Enhancement was not observed in rats pretreated with methylatropine or previously vagotomised. These results are compatible with interference by isoniazid with GABAergic inhibition of cardiac parasympathetic tone. Such interference could be exerted centrally, possibly at the nucleus ambiguus, or peripherally at the sinus node. [ABSTRACT FROM AUTHOR]

The endogenous compound hydroxylamine relaxes vascular smooth muscle in vitro, apparently through conversion to the vasodilator factor nitric oxide, but its effect on blood pressure has not been characterized. We found that in the anesthetized rat the amine elicits dose-related hypotension when administered by continuous iv infusion. In experiments designed to explore the mechanism of this effect, hydroxylamine was compared with the nitric oxide donor nitroprusside and the direct-acting vasodilator hydralazine, using pretreatments known to modify diverse mechanisms of vasodilation. Hydroxylamine hypotension was enhanced by the SSAO inhibitor isoniazid and the SSAO substrate methylamine, a pattern shared by hydralazine. Responses were blocked by the guanylate cyclase inhibitor methylene blue and were increased by the nitric oxide synthase inhibitor L-NAME, a pattern shared by nitroprusside. It was concluded that hydroxylamine exerts hypotension partly through conversion to nitric oxide and partly by a “hydralazine-like” mechanism involving SSAO inhibition. [ABSTRACT FROM AUTHOR]