ATP-mediated release of arachidonic acid metabolites from venular endothelium causes arteriolar dilation.
This study was designed to test the hypothesis that venular administration of ATP resulted in endothelium-dependent dilation of adjacent arterioles through a mechanism involving cyclooxygenase products. Forty-three male golden hamsters were anesthetized with pentobarbital sodium (60 mg/kg ip), and the cremaster muscle was prepared for in vivo microscopy. ATP (100 microM) injected into venules dilated adjacent arterioles from a mean diameter of 51 +/- 4 to 76 +/- 6 microm (P < 0.05, n = 6). To remove the source of endothelial-derived relaxing factors, the venules were then perfused with air bubbles to disrupt the endothelium. Resting arteriolar diameter was not altered after disruption of the venular endothelium (51 +/- 5 microm), and the responses to venular ATP infusions were significantly attenuated (59 +/- 4 microm, P < 0.05). To determine whether the relaxing factor was a cyclooxygenase product, ATP infusion studies were repeated in the absence and presence of indomethacin (28 microM). Under control conditions, ATP (100 microM) infusion into the venule caused an increase in mean arteriolar diameter from 55 +/- 4 to 78 +/- 3 microm (P < 0.05, n = 6). In the presence of indomethacin, mean resting arteriolar tone was not significantly altered (49 +/- 4 microm), and the response to ATP was significantly attenuated (54 +/- 4 microm, P < 0.05, n = 6). These studies show that increases in venular ATP concentrations stimulate the release of cyclooxygenase products, possibly from the venular endothelium, to vasodilate the adjacent arteriole.
Hammer
L W
LW
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA. lhammer@physiology.umsmed.edu
Ligon
A L
AL
Hester
R L
RL
D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D008647:Mesocricetus; D018482:Muscle, Skeletal / Q000098:blood supply; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014699:Venules / Q000187:drug effects / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D000255:Adenosine Triphosphate; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin