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 ( , 3 ± 13%) whereas P s for PSA ( ) decreased by 27 ± 8% (P < 0.005). In venules from females, Ado elevated by 44 ± 20% (P < 0.05), whereas in those from males, Ado reduced 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.

Adenosine A2A receptor modulation of juvenile female rat skeletal muscle microvessel permeability

“…The first result, contrary to expectation (43), was that basal permeability of venules was not higher than that of the arterioles. Indeed, this outcome is in contrast with that observed in other vascular beds (venular P s Ͼ arteriolar P s ) including adult (29,57) and juvenile porcine heart (24, 59) and skeletal muscles of adult male rat (48), mouse (48), guinea pig (43), and rabbit (50). The primary difference between the current study and those published previously is that the venous values are significantly lower than reported for other rodent skeletal muscle models (adult male) (57).…”

“…It is well known that, in skeletal muscle, ADO is an important local metabolic vasodilator (6,14,39). In addition to ADO having the capacity to regulate blood flow delivery, and hence exchange, by dilating feed arterioles, ADO has been shown recently to regulate the exchange of protein by mediating permeability changes in coronary microvessels (25,29,30,57).…”

“…The notion that microvascular exchange is a dynamic process has arisen from studies in a variety of microvascular models including frog (27) and rat (46) mesentery and pig heart (29). Despite the need for understanding the mechanisms controlling the distribution of substrates and wastes in this major tissue, little is known, given the difficulty of assessing flux and permeability in a thick tissue.…”

“…While the same receptors were shown to be present in coronary venules, ADO appeared to be without effect on venular P s (56). Expansion of the data set, facilitating analysis of the venule data by sex, demonstrated that, in fact, ADO decreased P s of venules from males and increased P s of venules from females (29). Recent preliminary studies in rats (28) demonstrated that P s responses to ADO depended on vessel type, maturity, and sex.…”

Cardiac purinergic signalling in health and disease

“…Sexual dimorphism in the permeability response of coronary microvessels to adenosine was described [457].…”