Sexual dimorphism in the hypotensive effect of the new NO donor [Ru(terpy)(bdq)NO+]3+ (TERPY) in spontaneusly hypertensive rats (SHR).

Abstract

The spontaneously hypertensive rat (SHR) is an experimental model of hypertension and oxidative stress. Sexual dimorphism interferes in both conditions, affecting nitric oxide (NO) bioavailability and the action of NO donors. The classic NO donor is sodium nitroprusside (SNP), which has potent vasodilatory action, but releases toxic metabolites. As an alternative, nitrosyl ruthenium complexes have been studied. Recent data show that the relaxation induced by the compound [Ru(terpy)(bdq)NO+]3+ (TERPY) is impaired in the in renal hypertensive rats (2K-1C) aortic rings and is normalized by antioxidants. There are no data concerning in vivo actions of the compound, nor in SHR. Therefore, the aim of the present work is to evaluate the role of sexual dimorphism in the potency and maximum relaxant effect of TERPY in SHR. In awake SHR and Wistar rats, mean arterial pressure will be accessed by direct method before, during and after TERPY (50 e 70 mg/Kg) and SNP (35 ¼g/Kg) infusion. The role of endogenous NO and oxidative stress on the cardiovascular effect of TERPY and SNP will be accessed by pre infusion of the following pharmacological tools: L-NAME (NOS inhibitor), TEMPOL (superoxide dismutase mimetic), and apocinin (NADPH oxidase inhibitor). Key words: nitric oxide donors, SHR, arterial pressure, endothelium vascular, oxidative stress, sexual dimorphism.