Glucose-induced intestinal vasodilation via adenosine A1 receptors requires nitric oxide but not K(+)(ATP) channels.
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.


CONCLUSIONS
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.
Matheson
Paul J
PJ
Department of Surgery, University of Louisville, Louisville, Kentucky 40292, USA. paul.matheson@louisville.edu
Li
Na
N
Harris
Patrick D
PD
Zakaria
El Rasheid
el R
Garrison
R Neal
RN
D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D005947:Glucose / Q000378:metabolism; D005905:Glyburide; D006940:Hyperemia / Q000378:metabolism; D007408:Intestinal Absorption; D007583:Jejunum / Q000098:blood supply* / Q000378:metabolism; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D018715:Microscopy, Video; D055806:Microvessels / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014664:Vasodilation; D014970:Xanthines; D019323:omega-N-Methylarginine
D058916:Adenosine A1 Receptor Antagonists; D054086:KATP Channels; D043682:Receptor, Adenosine A1; D014970:Xanthines; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019001:Nitric Oxide Synthase; D005947:Glucose; D005905:Glyburide
Circ Res. 1996 Feb;78(2):231-7
8575066
Am J Physiol Heart Circ Physiol. 2001 May;280(5):H2329-35
11299238
Am J Physiol Heart Circ Physiol. 2003 Jan;284(1):H204-14
12388293
Pharm Acta Helv. 1995 Mar;69(4):231-42
7651967
Circ Res. 1987 Aug;61(2):187-93
3621485
Am J Physiol. 1996 Sep;271(3 Pt 1):G454-60
8843770
Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H631-6
12750062
J Surg Res. 1999 Jun 1;84(1):57-63
10334890
Am J Physiol. 1992 Oct;263(4 Pt 1):G487-93
1415708
J Surg Res. 1995 Jun;58(6):687-92
7791347
Br J Pharmacol. 1997 Aug;121(7):1355-63
9257914
Am J Physiol Regul Integr Comp Physiol. 2002 Jun;282(6):R1696-709
12010752
Am J Physiol. 1989 Nov;257(5 Pt 1):G798-808
2512816
Am J Physiol. 1980 Feb;238(2):H220-5
7361917
Eur J Pharmacol. 2000 Jan 3;387(1):93-9
10633166
Br J Pharmacol. 2001 Oct;134(4):745-52
11606314
Naunyn Schmiedebergs Arch Pharmacol. 1995 Oct;352(4):412-8
8532069
Am J Physiol. 1995 Nov;269(5 Pt 2):H1672-8
7503264
Am J Physiol. 1976 Mar;230(3):583-9
1266961
J Surg Res. 1997 Oct;72(2):146-54
9356236
Brain Res. 2001 Jul 13;907(1-2):93-9
11430889
J Surg Res. 1998 Dec;80(2):357-64
9878338
Am J Physiol. 1990 Sep;259(3 Pt 2):H820-6
2118729
Cardiovasc Res. 2001 Oct;52(1):25-39
11557231
J Pharmacol Exp Ther. 1999 Nov;291(2):655-64
10525085
Am J Surg. 2004 Nov;188(5):526-31
15546564
Microvasc Res. 1976 Jan;11(1):103-10
1263858
Am J Physiol. 1997 Sep;273(3 Pt 1):L581-7
9316492
Circ Res. 1980 Jun;46(6):764-70
7379242
Circ Res. 1986 Oct;59(4):474-81
3791585
Am J Physiol. 1998 Aug;275(2):H542-50
9683443
J Physiol. 1999 Jan 1;514 ( Pt 1):151-62
9831723
J Pharmacol Exp Ther. 1995 Jul;274(1):300-6
7616413
Circ Res. 1994 Mar;74(3):471-6
8118955
Circulation. 1993 Jul;88(1):235-44
8319338
Br J Pharmacol. 2002 Jan;135(2):444-50
11815380
FASEB J. 1991 Sep;5(12):2668-76
1916091
J Cardiovasc Pharmacol. 2003 Jan;41(1):73-80
12500024