Sex-specific computational models of the spontaneously hypertensive rat kidneys: factors affecting nitric oxide bioavailability
Sullivan, Jennifer C.
Layton, Anita T.
MetadataShow full item record
Citation (published version)Ying Chen, Jennifer C Sullivan, Aurelie Edwards, Anita T Layton. 2017. "Sex-specific computational models of the spontaneously hypertensive rat kidneys: factors affecting nitric oxide bioavailability." AMERICAN JOURNAL OF PHYSIOLOGY: RENAL PHYSIOLOGY, Volume 313, Issue 2, pp. F174 - F183. https://doi.org/10.1152/ajprenal.00482.2016
Sex-specific computational models of the spontaneously hypertensive rat kidneys: factors affecting nitric oxide bioavailability. Am J Physiol Renal Physiol 313: F174 –F183, 2017. First published March 29, 2017; doi:10.1152/ajprenal.00482.2016.—The goals of this study were to 1) develop a computational model of solute transport and oxygenation in the kidney of the female spontaneously hypertensive rat (SHR), and 2) 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 (O2 ) 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 O2 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 PO2 levels. Other potential sex differences in SHR, including O2 production rate, are predicted to significantly impact oxidative stress levels, but effects on NO concentration and PO2 are limited.
Showing items related by title, author, creator and subject.
Klings, Elizabeth S.; Farber, Harrison W. (BioMed Central, 2001-7-13)Acute chest syndrome (ACS) of sickle cell disease (SCD) is characterized pathologically by vaso-occlusive processes that result from abnormal interactions between sickle red blood cells (RBCs), white blood cells (WBCs) ...
Bhattacharya, Bidisha; Chatterjee, Sujoy; Devine, William G.; Kobzik, Lester; Beeler, Aaron B.; Porco, John A.; Kramnik, Igor (2016-04-18)Drug-resistant bacteria represent a significant global threat. Given the dearth of new antibiotics, host-directed therapies (HDTs) are especially desirable. As IFN-gamma (IFNγ) plays a central role in host resistance to ...
Paz, Miguel Ángel (2018)BACKGROUND: Pulmonary Hypertension (PH) is a common form of high blood pressure in the lungs. It affects the pulmonary arteries, which normally allow blood to flow from the right heart to the lungs. Nitric Oxide (NO) is a ...