To study the role of the serotoninergic 5-HT2B receptor in the development of cardiac hypertrophy and its link with left ventricular superoxide anion generation in a mouse model of angiotensin II-induced hypertension.

Wild-type and 5-HT2B receptor knock-out (KO) mice were perfused with angiotensin II (0.2mg.kg-1.d-1) for 14 days with or without SB215505 (1mg.kg-1.d-1), an antagonist of the 5-HT2B receptor. Heart rate and blood pressure were measured by tail-cuff plethysmography. Cardiac hypertrophy was evaluated by echocardiography and direct measurement of heart weight. Superoxide anion production and maximal NAD(P)H oxidase activity were measured by a chemiluminescence method using lucigenin. Superoxide anion production was also measured in primary left ventricular fibroblasts cell cultures.

Angiotensin II increased superoxide anion production (+32 %), the maximal activity of NAD(P)H oxidase (+84 %) in left ventricle of wild-type mice concomitantly with the arterial blood pressure (+37mmHg) and the heart/body weight ratio (+17 %). A pharmacological blockade (SB215505) or a genetic suppression of the 5-HT2B receptor prevented the increased superoxide anion production and cardiac hypertrophy but had no effect on cardiac hemodynamics or blood pressure. Angiotensin II also increased NAD(P)H oxidase activity in cultured cardiac fibroblasts and this increase was prevented by SB215505.

The 5-HT2B receptor is a new potential target for the prevention of cardiac hypertrophy and its associated superoxide anion production. Cells of the extracellular matrix could possibly be involved in this mechanism.