Deoxycorticosterone suppresses the effects of losartan in nitric oxide-deficient hypertensive rats.
Chronic inhibition of the renin angiotensin system prevents increased BP and renal injury in N(G)-nitro-L-arginine methyl ester (L-NAME) hypertension. However, a relationship between plasma renin activity and the protective effect 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 losartan on BP, renal injury, and other variables in L-NAME hypertensive rats. The following groups were used: Control, DOCA, L-NAME, L-NAME + losartan, L-NAME + DOCA, and L-NAME + DOCA + losartan. Tail systolic BP was measured twice a week. After 4-wk evolution, mean arterial pressure and metabolic, morphologic, and renal variables were measured. The final mean arterial pressure 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 mmHg for L-NAME + DOCA, and 171 +/- 5.5 mmHg for L-NAME + DOCA + losartan. Losartan prevented microalbuminuria, hyaline arteriopathy, and glomerulosclerosis of L-NAME hypertension but was ineffective in L-NAME + DOCA-treated rats. Plasma protein was significantly reduced in the L-NAME + DOCA group when compared with control and L-NAME groups, whereas no significant differences were observed in the other groups. Plasma renin activity was suppressed in the DOCA (0.55 +/- 0.2) and L-NAME + DOCA (0.60 +/- 10.2) groups but unsuppressed 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 and renal injury of L-NAME hypertension, which suggests that DOCA transforms L-NAME hypertension into an Ang II-independent model of hypertension. These data also suggest that losartan prevents L-NAME hypertension by blocking the activity of systemic Ang II.
DE Gracia
Maria C
MC
Experimental Unit, Nephrology Service, Hospital Virgen de las Nieves, Granada, Spain.
Osuna
Antonio
A
Experimental Unit, Nephrology Service, Hospital Virgen de las Nieves, Granada, Spain.
O'Valle
Francisco
F
Department of Anatomical Pathology, Faculty of Medicine, Granada, Spain.
Del Moral
Raimundo G
RG
Department of Anatomical Pathology, Faculty of Medicine, Granada, Spain.
Wangensteen
Rosemary
R
Department of Physiology, Faculty of Medicine, Granada, Spain.
Del Rio
Cipriano Garcia
CG
Department of Physiology, Faculty of Medicine, Granada, Spain.
Vargas
Felix
F
Department of Physiology, Faculty of Medicine, Granada, Spain.
D000419:Albuminuria / Q000517:prevention & control; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000032:analysis; D003404:Creatinine / Q000097:blood; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D019808:Losartan / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000172:deficiency*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D012982:Sodium, Dietary
D001798:Blood Proteins; D004791:Enzyme Inhibitors; D012982:Sodium, Dietary; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D003404:Creatinine; D012083:Renin; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester