Increases of renal sodium transporters before and after the occurrence of the hypertension in spontaneously hypertensive rats

Abstract

Background: Adult spontaneously hypertensive rats (SHR) have increases of renal sodium transporters associated with hypertension. It remains to be determined whether the increases of renal sodium transporters are precede by occurrence of hypertension and reflected by urine exosomal sodium transporters that may serve as non-invasive biomarkers for the effcacy of anti-hypertensive drugs. Methods: 1. Male WKY rats and SHRs were aged of 4, 7 and 10 weeks respectively (n=5/group). 2. Additional 3 sets of 10-week-old rat (n=5/group) were administered by a 7-day intraperitoneal injections of furosemide (NKCC2 inhibitor, 5mg/kg), hydrochlorothiazide (NCC2 inhibitor, 30mg/kg) and amiloride (ENaC inhibitor, 10mg/kg) respectively. 3. The systolic blood pressure (SBP) was measured with a catheter in carotid artery of rats under anesthesia. Tail-cuff methods were used to monitor the drug responses. 4. All rats were rationally fed 0.4% NaCl agar-gelled diet for 7 days. 5. Exosomes were extracted with ultracentrifuge from the urines. Results: SHRs (4 weeks) exhibited similar SBP. The renal NKCC2, the major apical sodium transporters in thick ascending limb, was more than doubled in SHRs (215±14 % of WKY, student t-test, p<0.05, same as below) while the other sodium transporters were normal. However, SHRs had a higher SBP than WKY at ages of 7 (157±10 vs 125±14, mmHg) and 10 weeks (192±8 vs 128±12). There were no differences for the all age groups in heart rate, body weight, urine volume, urine Na+ and Cl− excretion, and serum Cr, K+, Na+, and Cl− concentration between rat strains. At 10-weeks old, renal (161±24) and urine exosomal (159±21, corrected by UCr, same as below) NKCC2 were higher in SHR than WKY. Frusemide normalized SBP on day 1 (day 0: 190±18 vs 138±13; day 1: 149±13 vs 128±16) in SHR; Renal (129±9) and urine-exosomal (137±12) NCC were higher in SHR than WKY. Hydrochlorothiazide normalized SBP in SHR on day 1 (day 0: 206±4 vs 140±9; day 1: 159±11 vs 144±11). Renal (α:134±16; β:137±25) and urine-exosomal (α:153±13; β:158±12) ENaCs were higher in SHR than WKY. Amiloride diminished the difference in SBP between rat strains on day 1 (day 0: 188±18 vs 138±11; day 1: 164±16 vs 147±7). Conclusions: The increase of renal NKCC2 precedes the elevation of SBP in SHRs. Urine exosomal NKCC2, NCC, ENaCs may reflect their renal levels and be indicative of the corresponding inhibitors on the hypertension model. Natural Science Foundation of China 81970605. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.