Title: Sexual dimorphism in the permeability response of coronary microvessels to adenosine
Abstract: Gender influences volume regulation via several mechanisms; whether these include microvascular exchange, especially in the heart, is not known. In response to adenosine (Ado), permeability ( P s ) to protein of coronary arterioles of female pigs decreases acutely. Whether Ado induces similar P s changes in arterioles from males or whether equivalent responses occur in coronary venules of either sex has not been determined. Hypotheses that 1) basal P s properties and 2) P s responses to vasoactive stimuli are sex independent were evaluated from measures of P s to two hydrophilic proteins, α-lactalbumin and porcine serum albumin (PSA), in arterioles and venules isolated from hearts of adult male and female pigs. Consistent with hypothesis 1, basal P s values of both microvessel types were independent of sex. Contrary to hypothesis 2, P s responses to Ado varied with sex, protein, and vessel type. Confirming earlier studies, Ado induced a ∼20% decrease in P s to both proteins in coronary arterioles from females. In arterioles from males, Ado did not change P s for α-lactalbumin ([Formula: see text], 3 ± 13%), whereas P s for PSA ([Formula: see text]) decreased by 27 ± 8% ( P < 0.005). In venules from females, Ado elevated [Formula: see text] by 44 ± 20% ( P < 0.05), whereas in those from males, Ado reduced [Formula: see text] 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.