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

Abstract

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 ( ΔMAP=10±1.4 mm Hg). Chronic SHR showed 60% increase ( ΔMAP=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 ( ΔMAP=30±2 mm Hg). (iii) The vasodilator response to Ach was increased in rats with Ang II-induced hypertension ( ΔMAP=53±1 mm Hg) and in SHR ( ΔMAP=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.