Fundamental microvascular processes were assumed to be sex-independent of until it was shown that flow & vascular tone are regulated differently by men & women; whether sex influences exchange is not known in spite of its importance in metabolic and volume homeostasis. Studies of coronary exchange in adaptation to exercise training show sex-dependent changes in both basal permeability (Ps) and Ps responses to the vasodilator, adenosine.
3 Aims are proposed to evaluate the hypothesis that sex hormones contribute to some, but not all, sex-specific differences in basal barrier properties and responses of the barrier to vasoactive stimuli. Barrier function will be quantified from measures of the essential determinants of volume homeostasis, hydraulic permeability (Landis technique) and protein permeability (microspectrofluorometry) under basal and stimulated conditions in arterioles and venules of muscle and mesentery (high vs. low metabolism) from juvenile (<40 d) and mature (>9 wk), hormone-defined, male and female rats.
In Aim I basal function in the 4 groups will be assessed to evaluate sex-hormone independent properties. As initial studies indicate sex-differences in permeability responses, Aim II evaluates function focusing on adenylyl and guanylyl cyclase pathways and evaluates the function and distribution of the vascular phosphodiesterase isoforms (PDE I-V) to define the sex-sensitive signaling mechanisms in the 4 groups.
In Aim III acute function will be evaluated with and without sex hormones to distinguish between genomic and non-gemomic actions. Sex hormone status will be evaluated for all animals to focus on the cellular and molecular mechanisms underlying sex-specific changes in exchange. This fundamental information on the dynamic nature of the microvessel barrier is essential to understanding volume and solute homeostasis in males & females in health (pre-syncopy on return to 1g; volume loss and restoration with exercise; menstrual cycle & pregnancy) and disease (higher mortality of male than female shock patients).
|Pelapur, Rengarajan; Prasath, V B Surya; Bunyak, Filiz et al. (2014) Multi-focus image fusion using epifluorescence microscopy for robust vascular segmentation. Conf Proc IEEE Eng Med Biol Soc 2014:4735-8|
|Lu, Xiao; Huxley, Virginia H; Kassab, Ghassan S (2013) Endothelial barrier dysfunction in diabetic conduit arteries: a novel method to quantify filtration. Am J Physiol Heart Circ Physiol 304:H398-405|
|Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H (2013) Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides. J Physiol 591:5071-81|
|Glinskii, Olga V; Huxley, Virginia H; Glinskii, Vladimir V et al. (2013) Pulsed estrogen therapy prevents post-OVX porcine dura mater microvascular network weakening via a PDGF-BB-dependent mechanism. PLoS One 8:e82900|
|Scallan, Joshua P; Huxley, Virginia H (2010) In vivo determination of collecting lymphatic vessel permeability to albumin: a role for lymphatics in exchange. J Physiol 588:243-54|
|Huxley, Virginia H; Wang, Jianjie (2010) Cardiovascular sex differences influencing microvascular exchange. Cardiovasc Res 87:230-42|
|Wang, Jianjie; Bingaman, Susan; Huxley, Virginia H (2010) Intrinsic sex-specific differences in microvascular endothelial cell phosphodiesterases. Am J Physiol Heart Circ Physiol 298:H1146-54|
|Glinskii, Olga V; Abraha, Tsghe W; Turk, James R et al. (2008) PDGF/VEGF system activation and angiogenesis following initial post ovariectomy meningeal microvessel loss. Cell Cycle 7:1385-90|
|Bunyak, F; Palaniappan, K; Glinskii, O et al. (2008) Epifluorescence-based quantitative microvasculature remodeling using geodesic level-sets and shape-based evolution. Conf Proc IEEE Eng Med Biol Soc 2008:3134-7|
|Huxley, Virginia H; Wang, Jian Jie; Sarelius, Ingrid H (2007) Adaptation of coronary microvascular exchange in arterioles and venules to exercise training and a role for sex in determining permeability responses. Am J Physiol Heart Circ Physiol 293:H1196-205|
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