This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. BACKGROUND AND HYPOTHESIS: Hypertension is associated with an increase of microvascular resistance, in part due to structural rarefaction defined by the anatomical loss of microvessels. Given that elevated blood pressure is accompanied and in some cases preceded by this loss of microvessels, therapies aimed at reversing rarefaction represent candidate treatments for hypertension. However, assessing the potential for such therapies and fully understanding microvascular dysfunction during hypertension requires a further mechanistic understanding of the relationship between network patterns and microvascular resistance. Preliminary data from our laboratory suggests that networks in the adult spontaneously hypertensive rat are marked by vessel loss, arterial/venous anastomoses, and reduced perivascular cell expression of Neuron-Glia Antigen 2 (NG2), a chondroitin sulfate proteoglycan recently implicated in endothelial cell proliferation and migration. Based on these observations, we hypothesize that reduced perivascular NG2 expression in hypertensive microvascular networks results in altered architectural patterns leading to elevated microvascular resistance. The following specific aims using the spontaneously hypertensive rat model were proposed for this subproject.
SPECIFIC AIMS :
AIM 1 : Evaluate microvascular network architecture and vessel-specific perivascular expression of NG2 over the time course of hypertension development.
AIM 2 : Determine if hypertensive microvascular network architectures result from altered perivascular NG2 expression.
AIM 3 : Determine the effect of hypertensive microvascular network architectures on microvascular network resistance and vessel specific hemodynamics. GOALS DURING YEAR 1 OF FUNDING For Year 1 of this subproject, we were allocated $55,607. The goals for Year 1 were to 1) collect additional preliminary data to be included in an R01 application;2) conclude ongoing projects that would then result in an increase in the number of hypertension related publications in order to strengthen the feasibility of work proposed in an R01 application;and 3) submit an R01 application directly related to the proposed COBRE subproject.
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|Hu, Tian; Yao, Lu; Reynolds, Kristi et al. (2016) Adherence to low-carbohydrate and low-fat diets in relation to weight loss and cardiovascular risk factors. Obes Sci Pract 2:24-31|
|Li, Wencheng; Sullivan, Michelle N; Zhang, Sheng et al. (2015) Intracerebroventricular infusion of the (Pro)renin receptor antagonist PRO20 attenuates deoxycorticosterone acetate-salt-induced hypertension. Hypertension 65:352-61|
|Li, Yuwen; Liu, Jiao; Li, Wencheng et al. (2015) p53 Enables metabolic fitness and self-renewal of nephron progenitor cells. Development 142:1228-41|
|Dobrowolski, Leszek; Kuczeriszka, Marta; Castillo, Alexander et al. (2015) Role of atrial natriuretic peptide in mediating the blood pressure-independent natriuresis elicited by systemic inhibition of nitric oxide. Pflugers Arch 467:833-41|
|Gonzalez, Alexis A; Prieto, Minolfa C (2015) Roles of collecting duct renin and (pro)renin receptor in hypertension: mini review. Ther Adv Cardiovasc Dis 9:191-200|
|Gonzalez, Alexis A; Prieto, Minolfa C (2015) Renin and the (pro)renin receptor in the renal collecting duct: Role in the pathogenesis of hypertension. Clin Exp Pharmacol Physiol 42:14-21|
|Hu, Tian; Yao, Lu; Reynolds, Kristi et al. (2015) The Effects of a Low-Carbohydrate Diet vs. a Low-Fat Diet on Novel Cardiovascular Risk Factors: A Randomized Controlled Trial. Nutrients 7:7978-94|
|Chen, Jing; Hamm, L Lee; Mohler, Emile R et al. (2015) Interrelationship of Multiple Endothelial Dysfunction Biomarkers with Chronic Kidney Disease. PLoS One 10:e0132047|
|Rivara, Matthew B; Ikizler, T Alp; Ellis, Charles D et al. (2015) Association of plasma F2-isoprostanes and isofurans concentrations with erythropoiesis-stimulating agent resistance in maintenance hemodialysis patients. BMC Nephrol 16:79|
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