Arteriolar constriction in skeletal muscle during vascular stunning: role of mast cells. Keller, Mark W. University of Colorado Health Sciences Center and the Denver Veterans Affairs Medical Center
APStracts 3:0526H, 1996.
Striated muscle becomes stunned during reperfusion following sub -lethal ischemia. Resistance vessel tone and reactivity are altered in stunned muscle tissues. The hypothesis that adenosine-regulated mast cell degranulation occurs during reperfusion and leads to constriction of resistance arterioles was tested. The hamster cremaster muscle was subjected to one hour of ischemia followed by reperfusion. Resistance arterioles constricted during reperfusion (diameters 74% of maximal diameter at baseline, vs. 42% of maximal diameter after 30 min reperfusion, p<0.01). Mast cells degranulated in reperfusion concomitant with arteriolar constriction. Stimulation of mast cell degranulation in control animals with compound 48/80 or cold superfusate (21 oC) caused vasoconstriction that mimicked that seen in reperfusion. Mast cell stabilizer cromolyn blocked degranulation and constriction. If mast cell granules were depleted by applying compound 48/80 prior to inducing ischemia, then arterioles failed to constrict during reperfusion. Adenosine A3 antagonist BW-A1433 abolished constriction. These findings suggest that arterioles constrict in reperfusion due to adenosine-regulated mast cell degranulation. Vasodilation in response to sodium nitroprusside and acetylcholine was normal in stunned, constricted arterioles. However, the dose-response curves to adenosine were shifted to the left in arterioles constricted by either stunning, compound 48/80, exposure to cold superfusate, or cromolyn compared to control vessels. Depletion of granular components via stunning, compound 48/80, cold superfusate, or inhibition of secretion with cromolyn, results in unopposed A1/A2 mediated vasodilation in response to adenosine, whereas the dilatory effects of adenosine are blunted by simultaneous release of vasoconstrictors from mast cells in control animals. In summary, it was found that mast cell degranulation occurs during reperfusion and leads to constriction of resistance arterioles and altered vascular reactivity to adenosine. Adenosine is released in ischemia and stimulates mast cell degranulation via the A3 receptor located on mast cells during reperfusion. 

Received 15 April 1996; accepted in final form 2 December 1996.
APS Manuscript Number H330-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996