Glucose-Induced Intestinal Vasodilation Via Adenosine A1 Receptors Requires Nitric Oxide but Not K+ATP Channels

• Published in: The Journal of surgical research 2011-06, Vol.168 (2), p.179-187
• Main Authors: Matheson, Paul J., Ph.D, Li, Na, M.D, Harris, Patrick D., Ph.D, Zakaria, El Rasheid, M.D., Ph.D, Garrison, R. Neal, M.D
• Format: Article
• Language: English
• Subjects: adenosine A1 receptor; ATP-dependent potassium channel; Biological and medical sciences; General aspects; glucose-induced intestinal hyperemia; intravital videomicroscopy; Medical sciences; nitric oxide; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2010.02.013

Background Both nitric oxide (NO) and adenosine A1 receptor activation mediate microvascular vasodilation during intestinal glucose absorption. Our overall hypothesis is that adenosine triphosphate (ATP) utilization during glucose absorption would increase adenosine metabolite release, which acts on adenosine A1 receptors to alter endothelial production of NO and/or activate ATP-dependent potassium channels (K+ATP ) to dilate intestinal microvessels. Methods Intravital videomicroscopy of the rat jejunum was used to record the vascular responses of inflow (termed 1A) arterioles, proximal (p3A), and distal (d3A) premucosal arterioles during exposure to isotonic glucose or mannitol solutions alone or in the presence of the selective nitric oxide synthase (NOS) inhibitor (L-NMMA), an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), or a K+ATP channel inhibitor (glibenclamide). Results As expected, glucose exposure caused rapid dilation of both p3A and d3A arterioles, while mannitol exposure had no effect on microvascular diameters. Adenosine A1 receptor blockade completely prevented glucose-induced dilation of the premucosal arterioles. NOS inhibition significantly blunted the glucose-induced vasodilation of the premucosal arterioles, but had little effect in the mannitol group. Simultaneous application of both the NOS inhibitor and the adenosine A1 receptor antagonist gave the same reduction in glucose-induced dilation of the premucosal arterioles as the adenosine A1 receptor antagonist alone. Blockade of K+ATP channels with glibenclamide did not attenuate glucose-induced vasodilation of the premucosal arterioles. Conclusion These data suggest that glucose-induced vasodilation of premucosal jejunal arterioles is mediated through adenosine A1 receptors, and NO at least partially mediates the adenosine A1 receptor-induced vasodilation. In addition, K+ATP channels are not involved in premucosal arteriolar vasodilation during intestinal glucose exposure.