Chronic alpha1-adrenergic blockade improves hypertension and renal injury in L-NAME and low-renin L-NAME-DOCA hypertensive rats.
BACKGROUND
The present study investigated the contribution of alpha1-adrenergic blockade to hypertension induced by long-term blockade of nitric oxide and chronic treatment with deoxycorticosterone acetate (DOCA), which produced a low renin model of hypertension. We studied the effects of chronic administration of prazosin, an alpha1-receptor antagonist, on blood pressure (BP), renal injury, and other variables in N(omega)-nitro-L-arginine methyl ester (L-NAME) and L-NAME+DOCA hypertensive rats.


METHODS
The rats were divided into 6 groups: Control, DOCA, L-NAME, L-NAME+DOCA, L-NAME+ prazosin, and L-NAME+DOCA+prazosin. Tail systolic BP was measured twice a week. After a 6-week evolution, mean arterial pressure (MAP) was measured, along with selected metabolic, morphological and renal variables.


RESULTS
The final MAP values were 105+/-1 for Control, 107+/-0.6 for DOCA, 153+/-3 for L-NAME, 175+/-2 for L-NAME+DOCA, 126+/-2 for L-NAME+prazosin and 127+/-5 for L-NAME+DOCA+prazosin. Proteinuria and hyaline arteriopathy were prevented in L-NAME+prazosin rats and markedly attenuated in the L-NAME+DOCA+prazosin group. Plasma urea and creatinine were significantly increased in the L-NAME+DOCA group, but not in the L-NAME+ DOCA+prazosin group as against controls. The DOCA and DOCA+L-NAME groups showed relative renal and cardiac hypertrophy, which was not observed in the DOCA+L-NAME+prazosin group.


CONCLUSIONS
Alpha1-adrenergic tone plays an important role in the increased BP and renal injury of L-NAME hypertension. Our results also indicate that when PRA is suppressed by DOCA in L-NAME hypertension, the increased BP and renal injury are largely dependent on the alpha1-adrenergic tone.
Wangensteen
Rosemary
R
Departamento de Fisiología, Facultad de Medicina, Granada, Spain.
O'Valle
Francisco
F
Del Moral
Raimundo
R
Vargas
Félix
F
Osuna
Antonio
A
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006977:Hypertension, Renal / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000293:injuries*; D007674:Kidney Diseases / Q000188:drug therapy; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D013997:Time Factors
D058668:Adrenergic alpha-1 Receptor Antagonists; D004791:Enzyme Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester