Abstract P135: Angiotensin II, But Not Methoxamine Or 5-HT, Causes ATP Release in the Rat Mesenteric Arterial Bed

Abstract

The control of vascular caliber relies on mediators released from multiple components of the vascular neuroeffector junction. These mediators include ATP, which is released from the sympathetic nerves from vesicles that also contain norepinephrine, as well as from the vascular smooth muscle (VSM) via pannexin-1 (panx-1) channels. We hypothesize that VSM-derived ATP plays a critical role in balancing the vasoactive effects of mediators at the vascular neuroeffector junction. Panx-1 channel opening on VSM has been reported to be stimulated by caspase cleavage, cytoplasmic Ca 2+ , and extracellular K + , but the effects of VSM GPCR activation are not as well characterized. Here we utilize a near-real time luminometric technique to quantify the release of ATP from the rat mesenteric arterial bed in response to vasoconstrictor agonists. We observed disparate effects of three physiologically relevant vasoactive agents, and these do not correlate with the relative changes in perfusion pressure. Whereas angiotensin II caused a robust release of ATP (228.6 ± 31.94 nM), no significant release was observed with either methoxamine (an α 1 agonist; 44.41 ± 31.94 nM) or 5-HT (0 ± 0 nM) . These results indicate that GPCR-mediated smooth muscle contraction is not sufficient to induce ATP release in this vascular bed. This is an important first step toward understanding the role of ATP in the vasculature.