Interaction with Pyridoxal as a Possible Mechanism of Hydralazine Hypotension

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Abstract
The mechanism by which the antihypertensive vasodilator hydralazine relaxes vascular smooth muscle is unknown. The drug interacts with pyridoxal and can produce B6 deficiency; it also inhibits a number of enzymes requiring pyridoxal as a cofactor, but there is no apparent relation between its enzymatic and blood pressure effects. To explore the possibility of a hydralazinepyridoxal interaction at a nonenzymatic site, the acute hypotensive response to hydralazine was determined by tail cuff blood pressure (BP) measurements in conscious normotensive rats pretreated or not pretreated with pyridoxine. Other animals were pretreated with isoniazid, a drug also capable of reacting with pyridoxal. Responses to hydralazine were diminished by pyridoxine and enhanced by isoniazid; those to the vasodilator diazoxide or to the α-adrenergic blocker zolertine were unaffected by such pretreatments. The inhibitory effect of pyridoxine was absent when rats were pretreated with the calcium antagonists verapamil or cinnarizine. Hydralazine hypotension in anesthetized rats was also reduced by pyridoxal pretreatment. These results suggest that at least part of hydralazine-induced hypotension may be related to interaction with pyridoxal, possibly through interference with an effect of the vitamer on calcium and/or sodium transport into vascular smooth muscle.