Mechanisms of increased sensitivity to A2 adenosine receptor stimulation in immature rabbit aortic rings.
Adenosine receptor-mediated vasodilation is increased in immature vessels compared to mature vessels. To determine the mechanism of this increased sensitivity, isolated vascular rings from mature and immature rabbits were studied to evaluate the contribution of the endothelium and the contribution of adenosine-dependent 3',5'-cyclic monophosphate (cAMP) to adenosine receptor-mediated relaxation. Dose responses were measured in endothelial-intact and nonendothelialized aortic rings using 5'-(N-ethylcarboxamido)-adenosine (NECA), a nonhydrolyzable adenosine agonist. Immature rings were more sensitive to NECA than mature rings as demonstrated by a lower ED50 and steeper slope of the dose-response curve. There was no effect on endothelial removal in immature rings while there was a significant decrease in response in mature rings. Despite being more sensitive to NECA, immature rings had less increase in cAMP (percent change from basal level) at maximal vasodilation than mature rings although cAMP did not change in either age at the ED50. The lack of change with endothelial removal in immature vessels suggests that the endothelium is not involved in the increased sensitivity of immature rings to NECA. The cAMP data suggests that other mechanisms for vasodilation are important at the ED50 for NECA in both ages. Maximal vasodilation with NECA on the other hand was associated with increases in cAMP although they were lower in the immature rings.
Matherne
G P
GP
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908.
Girling
P W
PW
McDaniel
N L
NL
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001013:Aorta, Thoracic / Q000254:growth & development* / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D013268:Stimulation, Chemical; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol