Renal Changes Induced by Nitric Oxide and Prostaglandin Synthesis Reduction
Male
Meclofenamic Acid
Indoles
Prostaglandin Antagonists
Angiotensin-Converting Enzyme Inhibitors
Blood Pressure
Calcium Channel Blockers
Kidney
Nitric Oxide
Renal Circulation
3. Good health
03 medical and health sciences
Dogs
NG-Nitroarginine Methyl Ester
0302 clinical medicine
Verapamil
Animals
Cyclooxygenase Inhibitors
Female
Enzyme Inhibitors
Glomerular Filtration Rate
DOI:
10.1161/01.hyp.31.2.657
Publication Date:
2012-06-12T00:53:46Z
AUTHORS (6)
ABSTRACT
Abstract
—The benefits of the simultaneous administration of low doses of a calcium antagonist and a converting enzyme inhibitor in the treatment of hypertension and renal vasoconstriction are well established. The objective of this study was to evaluate whether the administration of low doses of a calcium antagonist and a converting-enzyme inhibitor have beneficial effects in treating the renal alterations induced by the acute administration of a cyclooxygenase inhibitor when nitric oxide synthesis is reduced. These effects were examined in anesthetized dogs before and during an acute sodium load. It was found that the intrarenal infusion of meclofenamate (5 μg · kg
−1
· min
−1
), simultaneously with a low dose of
N
G
-nitro-
l
-arginine methyl ester (1 μg · kg
−1
· min
−1
), produced a 40% decrease of renal blood flow and glomerular filtration rate and a reduction in the renal excretory response to the sodium load. In a second group of dogs, intrarenal verapamil (0.5 μg · kg
−1
· min
−1
) was effective in blocking the effects of nitric oxide and prostaglandin synthesis inhibition on sodium excretion and glomerular filtration rate but did not modify the effects on renal blood flow. An intrarenal infusion of trandolapril (0.3 μg · kg
−1
· min
−1
) was effective in a third group of dogs in reducing the renal hemodynamic effects but not in preventing the antinatriuretic effect observed in the first group. Finally, in a fourth group, the simultaneous administration of verapamil and trandolapril was effective in treating all the renal changes induced by the cyclooxygenase inhibitor when nitric oxide synthesis was reduced. These results suggest that the combination of low doses of trandolapril and verapamil has additive effects in treating the renal vasoconstriction and antinatriuresis induced by the acute administration of a cyclooxygenase inhibitor, when nitric oxide synthesis is reduced.
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