Naloxone attenuates development of hypertension in DOCA-salt hypertensive rats

The effects of naloxone on the development of hypertension were studied in unilaterally nephrectomized rats implanted with deoxycorticosterone acetate (DOCA; 200 mg/kg) and given saline to drink. Intraperitoneal (i.p.) infusion of naloxone at 150 micrograms/hr significantly lowered systolic blood pressure (SBP) compared to rats not receiving naloxone, (135 +/- 4.4 vs 158 +/- 5.9 mmHg on day 16). IP infusion of naloxone at 300 micrograms/hr produced the same reductions of SBP as that at 150 micrograms/hr in DOCA-salt treated rats. In other experiments intracerebroventricular (i.c.v.) infusion of naloxone at 7 micrograms/hr also significantly attenuated the DOCA-salt hypertension. The same dose given i.p. had no effect on the development of hypertension. Naloxone had no effect on plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP), or concentrations of Na+ and K+ in plasma. The present data demonstrate that naloxone significantly attenuates the development of hypertension in rats given DOCA and fed a high salt diet. The attenuation of blood pressure could not be associated with the changes in PRA or plasma ANP. These results imply that the central opiate receptors play an important role in the pathogenesis of this model of hypertension.