BACKGROUND: Female humans and rodents are relatively protected against the development of hypertension and renal disease. Whether this protection is modified during insulin resistance and obesity, however, is not known. OBJECTIVE: Because renal sodium reabsorption has a central role in determining blood pressure, we hypothesized that lean female rats would bave reduced renal expression, activity, and urinary excretion of 8 major sodium transporters/channels. METHODS: Lean and obese, male and female Zucker rats (n = 4-8 per group) were fed progressively higher levels of dietary NaCl over a period of 54 days. Urinary excretion of renal sodium transport proteins was determined for 3 different dietary levels (0.04%, 0.4%, and 4%) of NaCl. With the high-NaCl diet, natriuretic responses to benzamil, furosemide, and thiazide were used as in vivo markers for activity of the epithelial sodium channel (ENaC), the bumetanide-sensitive Na-K-2C1 cotransporter (NKCC2), and the thiazide-sensitive NaCl cotransporter (NCC), respectively. RESULTS: Female rats (of both body types) had lower plasma renin activity and insulin levels than their male counterparts. Likewise, immunoblotting revealed female rats had increased whole kidney abundance of NCC and of the alpha, beta, and gamma subunits of ENaC, as well as decreased abundance of the type 3 sodium hydrogen exchanger (NHE3), type 2 sodium phosphate cotransporter (NaPi-2), and alpha-1 sodium-potassium-adenosine triphosphatase (Na-K-ATPase), compared with males. Obese rats had reduced levels of NKCC2, NHE3, and gamma-ENaC, but higher levels of NaPi-2 and NCC. Urine excretion of sodium transporters in lean female rats was nearly undetectable, whereas obese rats of both sexes excreted markedly more NKCC2 and NCC, which agreed with greater natriuretic responses to thiazide and furosemide. CONCLUSIONS: Obese female rats are similar to lean female rats with regard to the sex-distinct pattern of renal sodium transporters. However, obese female rats are more like obese male rats with regard to increased natriuretic response tofurosemide and thiazide, and to urine excretion of several transporters including NCC. Our results suggest that, with obesity, there is some loss of the protective female advantage.
BACKGROUND: Female humans and rodents are relatively protected against the development of hypertension and renal disease. Whether this protection is modified during insulin resistance and obesity, however, is not known. OBJECTIVE: Because renal sodium reabsorption has a central role in determining blood pressure, we hypothesized that lean female rats would bave reduced renal expression, activity, and urinary excretion of 8 major sodium transporters/channels. METHODS: Lean and obese, male and female Zucker rats (n = 4-8 per group) were fed progressively higher levels of dietary NaCl over a period of 54 days. Urinary excretion of renal sodium transport proteins was determined for 3 different dietary levels (0.04%, 0.4%, and 4%) of NaCl. With the high-NaCl diet, natriuretic responses to benzamil, furosemide, and thiazide were used as in vivo markers for activity of the epithelial sodium channel (ENaC), the bumetanide-sensitive Na-K-2C1 cotransporter (NKCC2), and the thiazide-sensitive NaCl cotransporter (NCC), respectively. RESULTS: Female rats (of both body types) had lower plasma renin activity and insulin levels than their male counterparts. Likewise, immunoblotting revealed female rats had increased whole kidney abundance of NCC and of the alpha, beta, and gamma subunits of ENaC, as well as decreased abundance of the type 3 sodium hydrogen exchanger (NHE3), type 2 sodium phosphate cotransporter (NaPi-2), and alpha-1 sodium-potassium-adenosine triphosphatase (Na-K-ATPase), compared with males. Obeserats had reduced levels of NKCC2, NHE3, and gamma-ENaC, but higher levels of NaPi-2 and NCC. Urine excretion of sodium transporters in lean female rats was nearly undetectable, whereas obeserats of both sexes excreted markedly more NKCC2 and NCC, which agreed with greater natriuretic responses to thiazide and furosemide. CONCLUSIONS:Obese female rats are similar to lean female rats with regard to the sex-distinct pattern of renal sodium transporters. However, obese female rats are more like obese male rats with regard to increased natriuretic response tofurosemide and thiazide, and to urine excretion of several transporters including NCC. Our results suggest that, with obesity, there is some loss of the protective female advantage.
Authors: Luciana C Veiras; Adriana C C Girardi; Joshua Curry; Lei Pei; Donna L Ralph; An Tran; Regiane C Castelo-Branco; Nuria Pastor-Soler; Cristina T Arranz; Alan S L Yu; Alicia A McDonough Journal: J Am Soc Nephrol Date: 2017-08-03 Impact factor: 10.121
Authors: Benjamin Ko; Kristin Bergsland; Daniel L Gillen; Andrew P Evan; Daniel L Clark; Jaime Baylock; Fredric L Coe; Elaine M Worcester Journal: Am J Physiol Regul Integr Comp Physiol Date: 2015-05-06 Impact factor: 3.619
Authors: Rolando Carrisoza-Gaytan; Evan C Ray; Daniel Flores; Allison L Marciszyn; Peng Wu; Leah Liu; Arohan R Subramanya; WenHui Wang; Shaohu Sheng; Lubika J Nkashama; Jingxin Chen; Edwin K Jackson; Stephanie M Mutchler; Szilvia Heja; Donald E Kohan; Lisa M Satlin; Thomas R Kleyman Journal: JCI Insight Date: 2020-04-07
Authors: Lei Wang; Ximing Wang; Helena Y Qu; Shan Jiang; Jie Zhang; Liying Fu; Jacentha Buggs; Bo Pang; Jin Wei; Ruisheng Liu Journal: Hypertension Date: 2017-10-23 Impact factor: 10.190