Presynaptic modulation of the release of noradrenaline from electrically stimulated bicuspid valve leaflet of the rabbit heart

Abstract

The bicuspid (mitral) valves were obtained from male albino New Zealand rabbits. The noradrenaline (NA) content (12.93 ± 1.14 nmol/g) of the valve tissue was determined by high pressure liquid chromatography (HPLC) combined with electrochemical detection. After incubation with tritiated NA for 45 min, the tissues were mounted in perfusion baths and superfused with Krebs solution at a constant perfusion rate. After a 90 min washing period, the tissues were stimulated three times (S 1;S 2;S 3) at a frequency of 1 or 10 Hz, and the release of NA was expressed as the stimulus-induced overflow of radioactivity. Using a constant number of impulses, the release of NA was significantly higher when the frequency applied was 10 Hz than in the case of 1 Hz. The release of NA was inhibited by stimulating the presynaptic α 2-adrenoceptors with xylazine or by stimulating the presynaptic muscarinic receptors with oxotremorine. Yohimbine (1 μM) not only overcame the effect of the α 2-adrenoceptor stimulation caused by xylazine, but increased it over the control level, whereas atropine blocked the inhibitory effect of oxotremorine. It is concluded that the adrenergic nerves in the valve tissue release NA in a frequency-dependent fashion, and the release of NA can be modulated through presynaptic α 2- and muscarinic receptors. This is the first case that neurochemical evidence was obtained showing that NA is released from the mitral valve and is subject to presynaptic modulation.