Abstract P283: Effects of High Salt Diet on Vascular Function and Renal Injury in a Novel Mouse Model of Neurogenic Hypertension

Abstract

In the brain, transcription of the renin gene is initiated from an alternative promoter within exon 1b resulting in the expression of Renin-b, a renin isoform lacking the signal peptide and first third of the prosegment. The specific deletion of Renin-b paradoxically induces neurogenic hypertension concomitant with increased brain renin-angiotensin system and renal sympathetic nerve activation. High dietary sodium intake has been associated with hypertension, endothelial dysfunction, and renal complications especially in salt-sensitive populations. We hypothesized that deletion of Renin-b causes vascular dysfunction and induces renal damage. In addition, high dietary sodium intake further exacerbates end-organ damage in Renin-b deficient mice (Ren-b KO). To evaluate vascular function, acetycholine (Ach) and nitroprusside (SNP)-induced dose-dependent vasorelaxation was assessed in aorta, carotid and basilar arteries isolated from Ren-b KO or littermate controls fed normal or high sodium diet (4% NaCl) for 4 weeks. Urinary protein excretion was measured at baseline and after 4 weeks on high sodium diet in control and Ren-b KO mice. At baseline, Ren-b KO exhibited impaired Ach-induced vasorelaxation in the aorta (logEC50 control: 0.88mM vs Ren-b KO: 1.1mM; p = 0.014; n=4) while SNP dose-response curve was unaltered. Urinary protein levels were increased in Ren-b KO (control: 11.0±3.7 vs Ren-b KO: 45.8±9.3 mg/day; p = 0.007; n=6-8). In control mice, 4 weeks high sodium diet increased urinary protein levels compared to baseline (baseline: 11.0±3.7 vs high salt: 31.6±7.4 mg/day); however high salt diet did not worsen proteinuria in Ren-b KO (baseline: 45.8±9.3 vs high salt: 44.1±4.5 mg/day). Similarly, Ren-b KO fed high sodium diet did not exhibit higher degrees of vascular dysfunction in comparison with control mice on high sodium diet. Our data indicates that Renin-b deletion promotes end-organ damage, likely as a consequence of high blood pressure or sympathetic nerve activation or both. Surprisingly, high sodium diet failed to exacerbate vascular dysfunction or proteinuria in Ren-b KO. Studies are in progress to evaluate the blood pressure response to high sodium diet in Ren-b KO mice to assess if Ren-b KO mice are salt sensitive.