Effect of Higenamine on ³H-Norepinephrine Release In the Rabbit Pulmonary Artery

Abstract

It has been reported that higenamine increased the cardiac output and the heart rate and decreased the systemic vascular resistance and blood pressure by stimulating (3 -adrenoceptors. This study was undertaken to investigate the effects of higenamine on the pre- and post-synaptic adrenergic neurotransmission in the spiral strips of pulmonary arteries of New Zealand white rabbits. As the pre-synaptic response, the spontaneous and stimulationinduced release of 3H-norepinephrine eH-NE), and as the post-synaptic response, the contractile response were measured. The results were as follows: 1. Higenamine (3 X 10-6, 3 X 10-5 and 10-4M) increased both spontaneous and stimulation- induced 3H-NE release dose-dependently, by 20-90% and 20-220%, respectively but decreased the contractile response in a dose-dependent manner. 2. The effect of higenamine in increase of spontaneous and stimulation-induced 3H-NE release was partially inhibited by the treatment of propranolol (3 X 10'--6M), but the effect in contractile response was completely blocked. Isoproterenol (1.3 X 10-8 , 1.3 X 10- 7 and 1.3 X 10-6M) had no effect on spontaneous and stimulation-induced 3H-NE release and contractile response. 3. The effect of higenamine was not inhibited by treatment with cocaine (3 X 10-5M). 4. The a z-adrenoceptor antagonist, yohimbine (3 X 10-8 and 3 X 10-7M) increased the stimulation-induced 3H-NE release but did not affect spontaneous release. 5. Papaverine (3 X 10-6, 3 X 10-5 and 10-4M) increased spontaneous and stimualtioninduced 3H-NE release in a dose-dependent manner. These results sugest that higenamine increases neurotransmitter release by the mechanism of presynaptic action through the enhancement of cyclic AMP level in addition to stimulation of the presynaptic (3 -receptor and that the mechanism of post-synaptic action of higenamine lies in the stimulation of (3 -adrenoceptors.