Lithium prevents saline deoxycorticosterone acetate (DOCA) hypertension in the rat.

Uni-nephrectomized rats drinking 1% saline instead of water, were given Doca intramuscularly, 50 mg/kg BW per week for 2 weeks. The mean blood pressure in the control group was 105 +/- 4 (+/- S.E.) mm Hg, whereas in the Doca-saline group it rose to 152 +/- 5.1 (p less than 0.001). Rats, similarly treated, were placed on daily intraperitoneal lithium injections of either of two doses: 1.5 or 3.0 mEq/kg BW per day. Their blood pressures, at the end of 2 weeks of treatment, were 117 +/- 2 mm Hg and 103 +/- 2.1, respectively (p less than 0.001 vs. lithium-untreated Doca-saline rats). Water-drinking rats, receiving daily intraperitoneal lithium (3 mEq/kg BW) for 2 weeks, had normal blood pressures, not different from the controls (104 +/- 11 mm Hg). The Doca-saline and Doca-saline-lithium (1.5 mEq/kg/day) groups had similar changes in mean daily body weight, plasma sodium, osmolality, and GFR. The renal beta-adrenergic receptor density in the Doca-saline-lithium rats was in the normal range, 51 +/- 4.5 mol/mg of protein. In the Doca-saline hypertensive rats, it was significantly lower, being 27.2 +/- 3 fmol/mg of protein, p less than 0.05. These renal plasma cell membrane beta-adrenergic receptors were characterized by direct tissue binding with (-)[3H]dihydroalprenolol. These results show that lithium prevents the development of hypertension in the Doca-saline rats. The effect of lithium on the sympathetic nervous system is a possible mechanism in the prevention of the Doca-saline hypertension.