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

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.

• Authors: Rosemary Wangensteen, Francisco O'Valle, Raimundo Del Moral, Félix Vargas, Antonio Osuna
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 8 Issue 9 Pg. BR378-84 (Sep 2002) ISSN: 1234-1010 [Print] United States
• PMID: 12221376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adrenergic alpha-1 Receptor Antagonists
• Animals
• Desoxycorticosterone (pharmacology)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology)
• Hypertension, Renal (drug therapy)
• Kidney (drug effects, 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