Protective effects of the angiotensin II type 1 (AT1) receptor blockade in low-renin deoxycorticosterone acetate (DOCA)-treated spontaneously hypertensive rats.
The present study evaluates the participation of oxidative stress, tissue angiotensin II (Ang II) and endothelin (ET) in the effects of losartan on blood pressure (BP), ventricular hypertrophy and renal injury in spontaneously hypertensive rats (SHRs), and explores how these effects are modified when spontaneous hypertension is transformed in a low-renin model by the administration of deoxycorticosterone acetate (DOCA). The following groups were used: SHR-control, SHR+DOCA, SHR+losartan and SHR+DOCA+losartan. Tail systolic BP was measured once a week. After 9 weeks of treatment, direct BP and metabolic, morphological, biochemical and renal variables were measured. DOCA administration to SHRs produced an increase in BP, ventricular hypertrophy, renal weight, proteinuria, renal histopathological lesions, urinary excretion of isoprostane F2alpha and ET levels in the renal cortex. Losartan reduced BP, plasma malondialdehyde levels, urinary excretion of isoprostane F2alpha, renal Ang II and renal and urinary levels of ET in the SHR and DOCA-treated SHR groups. Losartan increased plasma nitrite/nitrate in SHRs, but not in low-renin DOCA-treated SHRs. Losartan reduced ventricular hypertrophy and ventricular Ang II in SHRs, but not in DOCA-treated SHRs. Losartan significantly decreased proteinuria and renal injury in DOCA-treated SHRs. We conclude that (i) the DOCA-induced aggravation of hypertension, ventricular hypertrophy and renal injury in SHRs is accompanied by augmented oxidative stress and increased levels of ET in the renal cortex, which could contribute to their development; and (ii) losartan reduced oxidative stress and renal Ang II and ET in SHRs and DOCA-treated SHRs, which might contribute to its antihypertensive and renoprotective effects, regardless of renin status.
Chamorro
Virginia
V
Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain.
Wangensteen
Rosemary
R
Sainz
Juan
J
Duarte
Juan
J
O'Valle
Francisco
F
Osuna
Antonio
A
Vargas
Félix
F
D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000378:metabolism; D003900:Desoxycorticosterone; D016232:Endothelins / Q000032:analysis / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D028421:Isoprostanes / Q000652:urine; D007668:Kidney / Q000378:metabolism; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D016232:Endothelins; D028421:Isoprostanes; C438786:isoprostane F2alpha III; D000804:Angiotensin II; D003900:Desoxycorticosterone; D008315:Malondialdehyde; D012083:Renin; D019808:Losartan