title: Conducted dilations initiated by purines in arterioles are endothelium dependent and require endothelial Ca2+.
abstract: The signaling pathways underlying the regulation of vascular resistance by purines in intact microvessels and particularly in communication of remote vasomotor responses are unclear. One process by which remote regions of arterioles communicate is via transmission of signals axially along the vessel wall. In this study, we identified a pathway for local and conducted dilations initiated by purines. Adenosine (Ado) or ATP (bind P1 and P2 purinergic receptors, respectively) was micropipette applied to arterioles (maximum diameter approximately 40 microm) in the cheek pouch of anesthetized hamsters. Observations were made at the site of stimulation (local) or approximately 1200 microm upstream along the same vessel. P2 antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium and suramin) inhibited local constriction to ATP, whereas local and upstream dilations were unaffected. In contrast, during inhibition of P1 receptors (with xanthine amine congener) the local constriction was unchanged, whereas both local and upstream dilations to ATP were inhibited. Hydrolysis of ATP to Ado is implicated in the dilator response as blocking 5'-ectonucleotidase (with alpha,beta-methyleneadenosine 5'-diphosphate) attenuated ATP-induced dilations. After endothelium denudation, constriction to ATP was unchanged, but dilations to both ATP and Ado were inhibited, identifying endothelial cells (ECs) as the primary target for P1-mediated dilation. Purines increased EC Ca2+ locally and upstream. Chelation of EC Ca2+ (with BAPTA) abolished the local and upstream dilations to P1 receptor stimulation. Collectively, these data demonstrate that stimulation of P1 receptors on ECs produces a vasodilation that spreads to remote regions. There is an associated increase in EC Ca2+, which is a required signaling intermediate in the manifestation of both the local and axially communicated arteriolar dilations.
authors.affiliation: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Tasmia
authors.initials: T
authors.lastname: Duza
authors.forename: Ingrid H
authors.initials: IH
authors.lastname: Sarelius
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors; D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008647:Mesocricetus; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011687:Purines / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011687:Purines; D014970:Xanthines; D004533:Egtazic Acid; D013498:Suramin; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000241:Adenosine