Simvastatin reduces losartan‐induced nitric oxide production in spontaneously hypertensive rats (SHR)

Abstract

Patients with hypertension take antihypertensive agents and cholesterol lowering drugs; however, few studies describe the effects of the interaction of antihypertensive agents with statins. To investigate this, SHRs were fed 3 different diets: a) low salt (ls); b) high salt (hs); c) lipid-rich (lr) diet and/or treated with either losartan (LOS), simvastatin (SIM) or LOS combined with SIM for 4 weeks. We evaluated the role of nitric oxide (NO), prostacyclin (PGI2) and thromboxane (TXA2) on the effects of LOS (10mg/kg/day) and SIM (2mg/kg/day) and their combination in SHRs. The SHRs fed the ls, hs or lr diet had a 34 ± 2, 33 ± 4 and 43 ± 5 mmHg increase in BP respectively. Treating the SHRs with LOS alone decreased BP in the ls fed rats but had no effect on rats fed the hs or lr diet; however, LOS combined with SIM reduced BP in rats fed hs diet. Plasma NO levels tended to be lower in the lr fed rats when compared to the ls and hs groups. Treating rats with LOS alone increased NO in the ls and lr fed animal. However, SIM alone had no effect on NO levels but when SIM was given in combination with LOS, it completely abolished the effect of LOS in the ls fed rats and partially (34%) blocked LOS stimulated NO increase in the lr fed rats. SIM increased plasma PGI2 and TXA2 in all three diets. LOS alone had no effect on the prostaglandins (PGs) but it completely blocked SIM induced increases in the PGI2 and TXA2. Together these data suggest a contribution of endogenous NO and PGs in the antihypertensive effect of LOS and SIM in the SHR that may be affected by the type of diet. Supported, in part, by NIH grant S06GM08248-12 and Merck & Co.