Inosine-induced vasoconstriction is mediated by histamine and thromboxane derived from mast cells.
Mast cell degranulation has been shown to release products that cause arteriolar constriction. We previously reported that two nucleosides, adenosine and inosine, cause vasoconstriction of isolated hamster cheek pouch arterioles by stimulating degranulation of periarteriolar mast cells. The objectives of the present study were to characterize the nucleoside-dependent vasoconstriction in vivo and to determine the mediator or mediators responsible. We examined the vasomotor effect of inosine on arterioles in the cheek pouches of anesthetized hamsters (70 mg/kg pentobarbital sodium) in the control situation and in the presence of receptor antagonists for histamine (H1), thromboxane A2 (Tx), and leukotrienes (LT). Most experiments were carried out using inosine applied once locally via micropipette to arterioles and observing the subsequent response. Over a range of inosine concentrations from 10(-5) to 10(-3) M in the pipette, we observed a dose-dependent increase in the incidence and magnitude of constriction. In addition, mast cell staining with ruthenium red was observed after stimulation with inosine, an indication of mast cell degranulation. Neither the H1, Tx, nor LT antagonist alone had a significant effect on the vasomotor response to inosine. However, combined H1 and Tx blockade significantly reduced the incidence and magnitude of inosine-induced constriction. These data establish that inosine-induced constriction occurs in vivo and support the role of mast cells in this response. Furthermore they suggest that multiple mediators, primarily histamine and thromboxane, are responsible for the observed constriction.
Shepherd
R K
RK
Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville 22908, USA.
Duling
B R
BR
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000502:physiology*; D007288:Inosine / Q000494:pharmacology*; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008647:Mesocricetus; D009994:Osmolar Concentration; D012430:Ruthenium Red; D013928:Thromboxane A2 / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*; D014666:Vasomotor System / Q000187:drug effects
D015289:Leukotrienes; D012430:Ruthenium Red; D013928:Thromboxane A2; D007288:Inosine; D006632:Histamine