Impaired vascular responses to nitrite in hypertensive rat aortae

Abstract

Recent data demonstrate that nitrite is a physiological vasodilator, suggesting that impaired vascular responses to nitrite may be a causative factor for hypertension. However, little is known about the vasodilator effects of nitrite in hypertension. We investigated the relaxant effects of sodium nitrite in spontaneously hypertensive rat (SHR) aortae and the responses were compared to those of age‐matched normotensive Wistar Kyoto (WKY) rat aortae. Sodium nitrite elicited relaxation in WKY and SHR aortae, but with a lesser potency in SHR. In particular, sodium nitrite at concentrations that reflect plasma level of endogenous nitrite (< 1 μmol/L) elicited relaxation in WKY aortae but not in SHR aortae. Free radical scavenging with ascorbic acid normalized responses to sodium nitrite in SHR but had no effect in WKY. Nitric oxide synthase inhibition with Nω‐L‐arginine methyl ester abolished responses to lower concentrations, but not to higher concentrations (≥100 μmol/L), of sodium nitrite in WKY but had no effect in SHR rings. Cyclooxygenase inhibition with indomethacin marginally potentiated responses to sodium nitrite in WKY but markedly increased in SHR. These findings suggest that the relaxation responses to nitrite are impaired in SHR aortae, possibly coupled to increased production of free radicals. It is possible that this abnormality participates in the pathogenesis of hypertension.