Presynaptic regulation of norepinephrine release in a model of nonfailing hypertrophied myocardium.

Abstract

Dysregulation of cardiac norepinephrine release in heart failure has been linked to an impairment of presynaptic regulation. Although myocardial hypertrophy is a key finding in the development of heart failure, there are no data available regarding prejunctional modulation of sympathetic transmitter release in nonfailing hypertrophied myocardium. This study investigated norepinephrine release, induced by electrical field stimulation, in isolated rat hearts obtained from animals pretreated by suprarenal aortic banding (AB) or sham operation. Seven weeks following operation, substantial myocardial hypertrophy was observed in AB rats without evidence of cardiac decompensation. Cardiac norepinephrine release was negatively correlated with heart weight/body weight ratio in rats with AB. No such correlation was found in sham rats. Function of presynaptic alpha(2)-adrenoceptors and AT(1) receptors was tested utilizing specific receptor agonists and antagonists. UK 14,304 (alpha(2)-adrenoceptor stimulation) suppressed norepinephrine release in sham and AB hearts without difference between the groups. Conversely, rauwolscine (alpha(2)-adrenoceptor blockade) enhanced norepinephrine release in sham and AB hearts. Again, no difference between the groups was observed. The same was true for stimulation and blockade of AT(1) receptors with angiotensin II and candesartan. Presynaptic modulation of norepinephrine release via alpha(2)-adrenoceptors and AT(1) receptors is functional in nonfailing hypertrophied myocardium. Reduced norepinephrine release in hypertrophy may therefore indicate structural rather than functional alterations.