Nitric Oxide and Peripheral Adrenergic Neuromodulation

Abstract

Researches indicate that in resistance vessels nitric oxide (NO) attenuates adrenergic responses by a postjunctional action, but not by decreasing norepinephrine (NE) release. In the heart NO does not modulate the chronotropic response to adrenergic nerve stimulation, but does enhance NE overflow in association with coronary vasodilation and ischemia/reperfusion. By directly testing the effects of NO in a reductionist system such as cardiac synaptosomes, where no local reflex mechanisms come into play, a potent concentration-dependent biphasic effect of NO on adrenergic nerve endings is uncovered. Thus, findings on cardiac synaptosomes may help to explain the discrepancies in the literature on the modulatory effects of NO on adrenergic nerve function. NO could have both inhibitory and facilitatory prejunctional effects on vascular sympathetic neurotransmission. As considerable disagreement still exists as to whether NO facilitates or inhibits sympathetic neurotransmission and whether NO acts pre- or postjunctionally, the role of NO is examined by studying its effects on endogenous norepinephrine (NE) release in a prototypic peripheral resistance bed, in the whole heart, and in sympathetic nerve endings isolated from the heart (i.e., cardiac synaptosomes). These studies indicate that in resistance districts, NO modulates adrenergic responses, but not NE release.