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1 Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO, USA; Center for Gender Physiology, University of Missouri, Columbia, MO, USA
2 Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO, USA; Center for Gender Physiology, University of Missouri, Columbia, MO, USA
* To whom correspondence should be addressed. E-mail: huxleyv{at}health.missouri.edu.
Gender is recognized to influence volume regulation by several mechanisms; whether these include microvascular exchange, especially in the heart, is not known. In response to adenosine (ADO), a cell permeant by-product of ATP breakdown, permeability (Ps) to protein of coronary arterioles of female pigs decreases acutely. Whether ADO induces similar changes of Ps in arterioles from males or whether equivalent responses occur in coronary venules of either sex has not been determined. Two hypotheses, (I) that basal Ps properties, and (II) Ps responses to vasoactive stimuli, are sex-independent, were evaluated from measures of Ps to two hydrophilic proteins, 
-lactalbumin and porcine serum albumin (PSA), in arterioles (n=137) and venules (n=24) isolated from the hearts of adult male (N=27) and female (N=52) pigs. Consistent with Hypothesis I, basal Ps of both microvessel types were independent of sex. Contrary to Hypothesis II, Ps responses to ADO varied with sex, protein, and vessel type. Confirming earlier studies, ADO induced a ~20% decrease in Ps to both proteins in coronary arterioles from females. In arterioles from males ADO did not change Ps -lactalbumin (3±13% n=21) while PsPSA decreased by 27±8% (n=25, p<0.005). In venules from females ADO elevated PsPSA by 44±20%
(p<0.05) while in those from males ADO reduced PsPSA by 24±5% (p<0.05). The variety of outcomes is consistent with transvascular protein and protein-carried solute flux being regulated by multiple sex-dependent mechanisms in the heart and provides evidence of differences in exchange homeostasis of males and females in health and, likely, disease.
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