Nucleoside-induced arteriolar constriction: a mast cell-dependent response.
Adenosine (Ado) is a potent vasodilator that has occasionally been shown to cause vasoconstriction. Constrictor responses are generally attributed to A1-receptor stimulation or interactions with the renin-angiotensin system. We describe a previously unreported vasoconstrictor action of Ado and inosine (Ino) in hamster cheek pouch arterioles and examine the mechanism by which these nucleosides induce constriction. Arterioles were dissected from male Golden hamster cheek pouches, transferred to a 37 degrees C tissue chamber, and cannulated at both ends. Changes of luminal diameter in response to Ado were measured to generate cumulative concentration-response curves. The concentration-response curves were biphasic: 10(-6) M Ado elicited an intense, transient constriction, and higher concentrations induced dilator responses. Pretreatment with 8(p-sulfophenyl)theophylline, an Ado receptor antagonist, inhibited the dilator responses but did not alter the constriction. Inhibition of Ado uptake with S-(4-nitrobenzyl)-6-thio-inosine eliminated the constrictor response without altering dilator responses. Similar effects were found after pretreatment with an Ado deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride. Finally, Ino, a metabolite of Ado, induced constrictions of similar magnitude to those seen with Ado, but at higher concentrations. The constrictor response was focal in nature, suggesting discrete sites of action of Ado. Methylene blue staining after Ado application revealed degranulated mast cells closely associated with the vessel wall, indicating a possible role for mast cell degranulation in the constrictor response. Supporting this idea were the observations that inhibition of degranulation by 10 microM cromolyn blocked the constrictor response, and compound 48/80 (a mast cell secretagogue) caused constriction similar to that elicited by Ado.(ABSTRACT TRUNCATED AT 250 WORDS)
Doyle
M P
MP
Department of Molecular Physiology, University of Virginia Health Sciences Center, Charlottesville 22908.
Linden
J
J
Duling
B R
BR
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology*; D058892:Adenosine Deaminase Inhibitors; D000345:Affinity Labels / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007288:Inosine / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D008647:Mesocricetus; D008751:Methylene Blue; D009055:Mouth / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D058892:Adenosine Deaminase Inhibitors; D000345:Affinity Labels; D058915:Purinergic P1 Receptor Antagonists; D003189:p-Methoxy-N-methylphenethylamine; D013868:Thioinosine; C010192:9-(2-hydroxy-3-nonyl)adenine; D007288:Inosine; C001789:4-nitrobenzylthioinosine; D000225:Adenine; D000241:Adenosine; D008751:Methylene Blue