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(Hypertension. 1998;31:657-664.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Renal Changes Induced by Nitric Oxide and Prostaglandin Synthesis Reduction

Effects of Trandolapril and Verapamil

Maria T. Llinás; Juan D. González; Francisca Rodríguez; Eduardo Nava; Stefano Taddei; ; F. Javier Salazar

From I Clinica Medica, University of Pisa, Pisa, Italy (S.T.); and Departamento de Fisiología, Facultad de Medicina (M.T.L., J.D.G., F.R., E.N., F.J.S.), Murcia, Spain.

Correspondence to F. Javier Salazar, Departamento de Fisiología, Facultad de Medicina, 30100 Murcia, Spain. E-mail salazar{at}fcu.um.es

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.

Key Words: vasoconstriction • nitric oxide • prostaglandin • sodium sensitivity • calcium antagonists converting enzyme inhibitors

This article has been cited by other articles:

				M. T. Llinas, F. Rodriguez, C. Moreno, and F. J. Salazar Role of cyclooxygenase-2-derived metabolites and nitric oxide in regulating renal function Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2000; 279(5): R1641 - R1646. [Abstract] [Full Text] [PDF]