Chronic alpha1-adrenergic blockade improves hypertension and renal injury in L-NAME and low-renin L-NAME-DOCA hypertensive rats

Med Sci Monit. 2002 Sep;8(9):BR378-84.

Abstract

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.

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: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists*
  • 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 / metabolism
  • Renin / metabolism
  • Time Factors

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Enzyme Inhibitors
  • Receptors, Adrenergic, alpha-1
  • Nitric Oxide
  • Desoxycorticosterone
  • Renin
  • NG-Nitroarginine Methyl Ester