Antihypertensive drugs and catecholamine metabolism: effects of reserpine and hydralazine on tyrosine hydroxylase activity and norepinephrine concentrations in the spontaneously hypertensive rat.

The antihypertensive drugs, reserpine and hydralazine, produce different effects on tyrosine hydroxylase activity and norepinephrine levels in blood vessels and other tissues of the spontaneously hypertensive rat at doses which cause an equivalent reduction in blood pressure. Reserpine administration is associated with increased tyrosine hydroxylase activity in the mesenteric artery, mesenteric vein and adrenal, but the vasculature appears more sensitive to the effects of reserpine than the adrenal. This increase in tyrosine hydroxylase activity can be related to catecholamine depletion in the mesenteric artery, mesenteric vein and adrenal. Since chlorisondamine, a ganglionic blocking agent, diminished the ability of reserpine to increase tyrosine hydroxylase activity in the mesenteric artery and adrenal, it is likely that increased nerve activity is involved in regulation of the enzyme in both tissues. Hydralazine neither alters tyrosine hydroxylase activity in arteries or veins, nor depletes catecholamine levels in these tissues. In the adrenal, hydralazine increases tyrosine hydroxylase activity independently of any change in catecholamine levels. It would appear that changes in tyrosine hydroxylase activity produced by antihypertensive drugs are organ dependent and may involve both neuronal activity and amine depletion.