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Review
. 2018;1065:307-328.
doi: 10.1007/978-3-319-77932-4_20.

Sex-Specific Characteristics of the Microcirculation

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Free PMC article
Review

Sex-Specific Characteristics of the Microcirculation

Virginia H Huxley et al. Adv Exp Med Biol. .
Free PMC article

Abstract

The requirements of metabolizing tissue are both continuous and variable; accordingly, the microvasculature serving that tissue must be similarly dynamic. Just as it is recognized that males and females of the same species have differing metabolic requirements, is it not likely that the microvasculature serving these tissues will differ by sex? This section focusing on the constituents of the microcirculation identifies what is known presently about the role sex plays in matching metabolic demand with microvascular function and areas requiring additional study. Many of the identified sex differences are subtle and easily ignored. In the aggregate, though, they can profoundly alter phenotype, especially under stressful conditions including pregnancy, exercise, and disease states ranging from diabetes to heart failure. Although the features presently identified to "have sex" range from differences in growth, morphology, protein expression, and intracellular signaling, males and females alike achieve homeostasis, likely by different means. Studies of microvascular sexual dimorphism are also identifying age as an independent but interacting factor requiring additional attention. Overall, attempting to ignore either sex and/or age is inappropriate and will prevent the design and implementation of appropriate interventions to present, ameliorate, or correct microvascular dysfunction.

Keywords: Aquaporin; Arterioles; Barrier function; Blood flow regulation; Capillaries; Coronary microvascular dysfunction; Endothelium; Fibrinolysis; Fluid homeostasis; Glycocalyx; Hydrostatic pressure; Hypertension; Lymphatics; Microcirculation; Microvascular network; Myogenic response; Orthostatic intolerance; Pericyte; Peripheral resistance; Pregnancy; Rarefaction; Sepsis; Sex difference; Sexual dimorphism; Syndecan-1; Vascular homeostasis; Venules.

Figures

Fig. 20.1
Fig. 20.1
Diagram of sexually dimorphic constituents identified in male and female humans influencing the three primary functions of the microvasculature:

Control of blood flow via changes in VSM tone of the arterioles

Control of gas, fluid, and solute exchange via changes in capillary barrier function

Control of inflammation and immune function in the venules

Overall, hydrostatic pressures, Part, Pcap and Pven, and VSM tone are higher in males than females reflecting in part the relatively higher levels of vasoconstrictors (ET-1) to vasodilators (BNP, NO) in the blood of males. Blood from males carries a greater number of red blood cells; while the amount of hemoglobin per cell does not vary greatly by sex, the larger number of cells means a higher net Hgb and thus a higher O2 carrying capacity favoring a higher O2 delivery in males. The higher protein content of plasma in the males results in a higher oncotic protein force that will offset the higher fluid movement out of the capillaries by Pcap in males. The number of platelets tends to be higher in females than males suggesting a higher tendency for formation of clots in females than males. While white cell numbers tend to be higher or not different between males and females, it is the sex differences in receptor density that appears to play a role in sex differences in WBC responses. On exposure to LPS, neutrophils via TLR4 receptor activation release greater amounts of the cytokine TNFa in males than females. Macrophages of females express higher ERa and ERb receptors; the response to LPS is mediated by ERa in both sexes but to a greater extent in females. Abbreviations: art arterioler, BNP B-type natriuretic peptide, cap capillary, ERa estrogen receptor alpha, ERb estrogen receptor beta, Hgb hemoglobin, LPS lipopolysaccharide, NO nitric oxide, TLR Toll-like receptor, TNFa tumor necrosis factor alpha, ven venule, VSM vascular smooth muscle, WBC white blood cell (count) Table 20.1 has most of these data (not the macrophage (Campesi et al., 2017) or neutrophil (Aomatsu et al., 2013) data, though) Aomatsu M, Kato T, Kasahara E, Kitagawa S. Gender difference in tumor necrosis factor-α production in human neutrophils stimulated by lipopolysaccharide and interferon-γ. Biochem Biophys Res Commun. 2013;441:220–5. Campesi J, Marino M, Montella A, Pais S, FranconiiF. Sex differences in estrogen receptor α and β levels and activation status in LPS-stimulated human macrophages. J Cell Physiol. 2017;232:340–5.

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