Production and reversal of DOCA-salt hypertension in baboons

We describe for the first time a non-human primate model of mineralocorticoid-salt hypertension. Baboons instrumented for chronic, direct measurement of arterial pressure, underwent sodium chloride loading (8.6 or 17.1 mEq/kg/day) by different routes for several weeks and deoxycorticosterone acetate (DOCA) 5 mg/2 days i.m., in addition to sodium chloride, for periods lasting up to several months. Salt loading alone at 8.6 mEq/kg/day had no chronic effect on mean arterial pressure (MAP). Salt loading at both doses in combination with DOCA produced increases in MAP within a few days which became progressively larger over weeks to months. DOCA-salt hypertension was associated with hyporeninemia and mild hypokalemia, without consistent changes in heart rate or plasma catecholamines. A biofeedback procedure applied to three animals failed to reduce tonic blood pressure. In two of these animals, administration of clonidine or atenolol also had no antihypertensive effect, whereas a diuretic combination (hydrochlorothiazide and triamterene) rapidly abolished the hypertension. The absence of amelioration of the hypertension by a central sympatholytic agent or a beta-adrenoceptor blocker, coupled with the absence of increased plasma catecholamines, suggests that increased sympathetic activity may not contribute to the hypertension in contrast with findings in lower animals but consistent with clinical reports.