Abstract
Abstract P247: Altered Renal Sodium Transporters Expression Is Associated With Cholinergic-mediated Salt Sensitive Hypertension In Young Spontaneously Hypertensive Rats
Hypertension (Dallas, Tex. 1979), Vol.79(Suppl_1)
09/2022
DOI: 10.1161/hyp.79.suppl_1.P247
Abstract
High sodium diet is a major contributing factor and has been associated with inflammation in patients suffering from hypertension. Systemic infusion of nicotine induces renal inflammation and the development of premature hypertension in young spontaneously hypertensive rats (SHR) and leads to enhanced expression of the renal Na-K-Cl cotransporter (NKCC2). Sodium sensitivity also plays a role in the development of cholinergic hypertension. We hypothesized that these findings were related to alterations in renal sodium transporters expression. We continuously infused SHR and Wistar Kyoto (WKY, normotensive control) rats with saline or nicotine (15mg/kg/day) and fed either a low-salt (LSD, 0.01% NaCl) or high-salt (HSD, 4% NaCl) diet for 2 weeks. Renal homogenates were assessed by western blot for the presence of the epithelial sodium channel (ENaC), NKCC2, Na-Cl co-transporter (NCC) and Serum and glucocorticoid regulated kinase 1 (SGK-1). Nicotine infusion in WKY induced 1.9-fold increase (p=0.003) in renal expression of SGK-1 under LSD, compared to saline-infused controls. The sharp increase in SGK-1 in nicotine-infused WKY on LSD was accompanied by a 1.9-fold increase in NCC (p=0.004), a 1.3-fold increase in the cleaved alpha ENaC, a 1.2-fold increase in the uncleaved alpha ENaC, and a 1.5-fold increase in the beta-ENaC (p=0.02). Both saline and nicotine infused WKY showed very little expression of renal NKCC2 in either LSD or HSD. There was no effect of either diet or nicotine infusion on expression of SGK-1, NCC, or ENaC subunits in SHR. Nicotine had no effect on NKCC2 expression in SHR on LSD, but HSD alone induced a 2.25-fold increase in renal NKCC2 expression compared to LSD in saline infused SHR (p=0.006). Nicotine infusion further induced a 58% increase in renal NKCC2 expression for SHR fed HSD (p=0.004). Here we show an effect of nicotine to appropriately increase the expression of NCC and ENaC in WKY under LSD and a trend towards decreased expression under HSD. In contrast, nicotine not only has no effect on NCC and ENaC under LSD in SHR but leads to a paradoxical increase in NKCC2 under HSD. We conclude that inappropriate regulation of renal sodium transporters likely plays a role in cholinergic-mediated renal inflammation and hypertension.
Details
- Title: Subtitle
- Abstract P247: Altered Renal Sodium Transporters Expression Is Associated With Cholinergic-mediated Salt Sensitive Hypertension In Young Spontaneously Hypertensive Rats
- Creators
- Nandita Raikwar - University of IowaTrever Maiers - Iowa City, IASailesh Harwani - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.79(Suppl_1)
- DOI
- 10.1161/hyp.79.suppl_1.P247
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 09/2022
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984362743502771
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