title: Sex-specific computational models of the spontaneously hypertensive rat kidneys: factors affecting nitric oxide bioavailability.
abstract: The goals of this study were to1) develop a computational model of solute transport and oxygenation in the kidney of the female spontaneously hypertensive rat (SHR), and2) apply that model to investigate sex differences in nitric oxide (NO) levels in SHR and their effects on medullary oxygenation and oxidative stress. To accomplish these goals, we first measured NO synthase (NOS) 1 and NOS3 protein expression levels in total renal microvessels of male and female SHR. We found that the expression of both NOS1 and NOS3 is higher in the renal vasculature of females compared with males. To predict the implications of that finding on medullary oxygenation and oxidative stress levels, we developed a detailed computational model of the female SHR kidney. The model was based on a published male kidney model and represents solute transport and the biochemical reactions among O2, NO, and superoxide ([Formula: see text]) in the renal medulla. Model simulations conducted using both male and female SHR kidney models predicted significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and [Formula: see text] concentration in the outer medulla and upper inner medulla. The models also predicted that increases in endothelial NO-generating capacity, even when limited to specific vascular segments, may substantially raise medullary NO and Po2levels. Other potential sex differences in SHR, including [Formula: see text] production rate, are predicted to significantly impact oxidative stress levels, but effects on NO concentration and Po2are limited.
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Physiology, Augusta University, Augusta, Georgia.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Sullivan
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Université Paris Descartes, Sorbonne Paris, France.|INSERM UMRS 1138, CNRS ERL 8228, Centre de Recherche des Cordeliers, Paris, France; and.|Department of Biomedical Engineering, Boston University, Boston, Massachusetts.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Edwards
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina; alayton@math.duke.edu.
authors.forename: Anita T
authors.initials: AT
authors.lastname: Layton
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure; D003198:Computer Simulation; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D055806:Microvessels / Q000201:enzymology; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D010100:Oxygen
keywords: gender; hypertension; nitric oxide; oxidative stress; reactive oxygen species; sex differences