Chronic alpha1-adrenergic blockade improves hypertension and renal injury in L-NAME and low-renin L-NAME-DOCA hypertensive rats
Rosemary Wangensteen, Francisco O’Valle, Raimundo G. Del Moral, Félix Vargas, Antonio Osuna
Med Sci Monit 2002; 8(9): BR378-384
Background: The present study investigated the contribution of α1-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 α1-receptor antagonist, on blood pressure (BP), renal injury, and other variables in Nω-nitro-L-arginine methyl ester (L-NAME) and LNAME+
DOCA hypertensive rats.
Material/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: α1-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 α1-adrenergic tone.
Keywords: Animals, Desoxycorticosterone - pharmacology, Disease Models, Animal, Enzyme Inhibitors - pharmacology, Hypertension, Renal - drug therapy, Kidney - drug effects, Kidney - injuries, Kidney Diseases - drug therapy, Kidney Glomerulus - pathology, Male, NG-Nitroarginine Methyl Ester - pharmacology, Nitric Oxide - antagonists & inhibitors, Rats, Rats, Wistar, Receptors, Adrenergic, alpha-1 - antagonists & inhibitors, Receptors, Adrenergic, alpha-1 - metabolism, Renin - metabolism, Time Factors