Central and Peripheral Indices of Sympathetic Activity After Blood Pressure Lowering with Enalapril (MK-421) or Hydralazine in Normotensive Rats

Various antihypertensive drugs have different effects on vasoactive mechanisms. In normotensive Wistar rats, we investigated the effects on plasma and tissue catecholamines of chronic treatment with two agents: MK-421, an angiotensin converting-enzyme inhibitor (CEI), and hydralazine, a vascular smooth muscle relaxant. Both agents lowered blood pressure via arteriolar dilation, to the same final level. However, hydralazine stimulated the renin-angiotensin system and elevated the plasma norepinephrine (NE) and epinephrine (E) levels, whereas MK-421 did not. In MK-421-treated animals, NE, E, and the ratio of E/NE were decreased in the brain stem, and this ratio was increased in the heart. In hydralazine-treated rats, the catecholamine levels were unchanged in the brain stem and heart. The turnover rate of NE was significantly reduced in the brain stem and heart of MK-421-treated rats, whereas, after hydralazine, the turnover rate in the heart was increased (decreasing the half-life of NE by about 50%), indicating increased sympathetic activity. Thus, elimination of angiotensin II (AII) by CEI is associated with decreased sympathetic activity in both the brain stem and heart, whereas an equipotent antihypertensive action by smooth muscle relaxation leads to stimulation of both the renin-angiotensin and the sympathetic systems. These differences are more readily apparent by measurement of catecholamine turnover rates in tissues than of catecholamine levels, and they may account for the different hemodynamic effects of the two agents, even though both drugs act through arteriolar dilation.