Deoxycorticosterone suppresses the effects of losartan in nitric oxide-deficient hypertensive rats

Chronic inhibition of the renin angiotensin system prevents increased BP an d renal injury in N-G-nitro-L-arginine methyl ester (L-NAME) hypertension. However, a relationship between plasma renin activity and the protective ef fect of chronic angiotensin II (Ang II) blockade has not been established. With this background, this study was undertaken to evaluate how the chronic administration of deoxycortisone acetate (DOCA) modifies the effects of lo sartan on BP, renal injury, acid other variables in L-NAME hypertensive rat s. The following groups were used: Control, DOCA, L-NAME, L-NAME + losartan , L-NAME + DOCA, and L-NAME + DOCA + losartan. Tail systolic BP was measure d twice a week. After 4-wk evolution, mean arterial pressure and metabolic, morphologic, and renal variables were measured. The final mean arterial pr essure values were 116 +/- 6 mmHg for control, 107 +/- 2 mmHg for DOCA, 151 +/- 5 mmHg for L-NAME, 123 +/- 2 mmHg for L-NAME + losartan, 170 +/- 3 mmH g for L-NAME + DOCA, and 171 +/- 5.5 mmHg for L-NAME + DOCA + losartan. Los artan prevented microalbuminuria, hyaline arteriopathy, and glomerulosclero sis of L-NAME hypertension but was ineffective in L-NAME + DOCA-treated rat s. Plasma protein was significantly reduced in the L-NAME + DOCA group when compared with control and L-NAME groups, whereas no significant difference s were observed in the other groups. Plasma renin activity was suppressed i n the DOCA (0.55 +/- 0.2) and L-NAME + DOCA (0.60 +/- 10.2) groups but unsu ppressed in the L-NAME + DOCA + losartan group (5.8 +/- 1). The conclusion is that DOCA blocks the preventive effect of losartan on the increased BP a nd renal injury of L-NAME hypertension, which suggests that DOCA transforms L-NAME hypertension into an Ang II-independent model of hypertension. Thes e data also suggest that losartan prevents L-NAME hypertension by blocking the activity of systemic Ang II.