A new inorganic vasodilator, trans-[Ru(NO)(NH(3))(4)(POEt)(3)](PF(6))(3): hypotensive effect of endothelium-dependent and -independent vasodilators in different hypertensive animals models

• Published in: Nitric oxide 2002-08, Vol.7 (1), p.50-56
• Main Authors: de Barros, Brígida Figueiredo, Toledo, Jr, José Carlos, Franco, Douglas Wagner, Tfouni, Elia, Krieger, Marta Helena
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Blood Pressure - drug effects; Disease Models, Animal; Endothelium, Vascular - physiology; Hypertension - drug therapy; Male; Nitric Oxide Donors - administration & dosage; Nitric Oxide Donors - pharmacology; Nitroprusside - pharmacology; Organometallic Compounds - administration & dosage; Organometallic Compounds - pharmacology; Rats; Rats, Wistar; Ruthenium Compounds - administration & dosage; Ruthenium Compounds - pharmacology; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacology
• ISSN: 1089-8603
• DOI: 10.1016/S1089-8603(02)00007-1

The hypotensive effect of RuNO was investigated in acute and chronic hypertensive rats, as well as in normotensive rats. Acute hypertension rats were used with 30% increase on basal BP (phenylephrine, angiotensin II (Ang II), N(G)-nitro-L-arginine methyl ester (L-NAME), and adult spontaneously hypertensive rats (SHR) (basal BP 168 +/- 3 mm Hg) were used as models for chronic hypertension. Rats were implanted with catheters (iv/ia) for BP measurements and for in bolus administration of RuNO, sodium nitroprusside (SNP), and acetylcholine (Ach) (10, 20, 40 nmol/kg, iv). The principal findings of this study were: (i) The hypotensive response to RuNO was 150% higher in acutely (phenylephrine and Ang II) and chronically (SHR) hypertensive rats than in normotensive rats, except in the case of L-NAME-induced hypertension (deltaMAP = 10 +/- 1.4 mm Hg). Chronic SHR showed 60% increase (deltaMAP = 19 +/- 0.8 mm Hg) in the effect compared to normotensive rats. (ii) The hypotensive response to SNP was lower (60%) in hypertensive rats than in normotensive rats, when compared to RuNO. However, the responses were similar in L-NAME-induced hypertension (deltaMAP = 30 +/- 2 mm Hg). (iii) The vasodilator response to Ach was increased in rats with Ang II-induced hypertension (deltaMAP = 53 +/- 1 mm Hg) and in SHR (deltaMAP = 67 +/- 3 mm Hg). RuNO response was more potent than SNP in hypertensive models and the increment in relation to normotensive was observed in the phenylephrine- and L-NAME-treated rats. This response could be correlated to the different endothelial dysfunction present in each model.