Effects on the Renin-Anglotensin System of Agents Acting at Central and Peripheral Adrenergic Receptors

¹ From the Hypertension Center, Veterans Administration Medical Center, Long Beach, California, and the University of California, Irvine

Although the principal actions of clonidine are linked to its centrally mediated suppression of sympathetic activity, its inhibition of the renin axis also may contribute to its antihypertensive effects. In patients with essential hypertension studied in a clinical research center, clonidine-induced decreases in diastolic blood pressure and in plasma renin activity (PRA) correlated closely after one day of treatment, but not thereafter. Moreover, high-renin patients experienced significantly greater blood pressure decrements than low-renin patients during the first day of treatment, but subsequent blood pressure decreases were equal in the two groups, confirming that the sympathoinhibitory action of clonidine is probably independent of the renin-angiotensin system. However, responders to clonidine treatment exhibited significantly greater decrements in aldosterone excretion rate than nonresponders. When compared with propranolol in an outpatient study, clonidine reduced aldosterone levels to the same extent as propranolol despite a significantly weaker inhibitory effect on PRA. Indeed, in a further comparative study with prazosin, during which neither agent decreased renin levels, clonidine significantly lowered aldosterone excretion. Thus, clonidine appears to have two separate actions on the renin-aldosterone axis: an early antirenin action primarily in high-renin patients, and a longer-term suppressive effect on aldosterone. This latter action is possibly independent of changes in renin, and perhaps reflects an effect on aldosterone release mediated through central mechanisms.