CONTROL OF NOREPINEPHRINE SYNTHESIS IN BLOOD VESSELS AND THE EFFECTS OF MONOAMINE OXIDASE INHIBITION

¹ Pharmacology Section, Roche Institute of Molecular Biology, Nutley, New Jersey

The aim of these studies was to examine end product regulation of norepinephrine (NE) synthesis in the vasculature. NE inhibits vascular tyrosine hydroxylase both in vivo and in vitro. However, in the intact guinea pig, elevation of NE levels after pargyline resulted in a 70 to 80% inhibition of NE synthesis in the heart, aorta and mesenteric vein whereas the synthesis of NE in the mesenteric artery was inhibited only 46% or less. We propose that in the heart, aorta and mesenteric vein, the NE storage capacity is rapidly filled after monoamine oxidase inhibition and that NE which is not bound readily inhibits tyrosine hydroxylase. In the mesenteric artery and presumably other densely innervated arteries where the tyrosine hydroxylase activity is very high, the larger reserve NE storage capacity limits the amount of catecholamine which can be achieved in the immediate vicinity of tyrosine hydroxylase. The result is that feedback inhibition by end product and the effects of pargyline vary in different parts of the cardiovascular system with arteries being the least sensitive.