Attenuation of methylation of catecholamines and treatment with a coenzyme of catechol-O-methyltransferase in spontaneously hypertensive rats (SHR)

Abstract

We have previously demonstrated that the release of plasma norepinephrine (NE) in response to blood pressure reduction induced by calcium antagonist was substantially decreased in spontaneously hypertensive rats (SHR), as compared to the age-matched normotensive Wistar Kyoto (WKY) rats. Here we examined extraneuronal methylation of NE to normetanephrine (NMN) by catechol-O-methyltransferase (COMT). In the face of an acute hypotension by benidipine, the ratio of the increase of NMN to the increase of NE in plasma was lower in SHR than in WKY rat. The finding suggests that the extraneuronal inactivation of the released NE is blunted in SHR, namely, COMT is deactivated in this hypertensive rats. To define the role of NE methylation in hypertension, S-adenosyl-L-methionine (SAMe; 1.0mg/kg, iv.), a coenzyme of COMT, was administered to SHR. The treatment induced a greater antihypertensive effect, along with a greater decrease of NE and a larger increase of NMN in SHR. The data suggest that SAMe may be used as a possible remedy for hypertension.