Impact of Afferent vs Total Renal Nerve Denervation on Cardiovascular Parameters in Male and Female Sprague Dawley Rats on Fructose- High Salt Diet

Consumption of combined fructose with high salt diet increases blood pressure, aortic stiffness, and cardiac fibrosis. We tested the hypothesis that selective denervation of renal afferent nerves or total denervation of renal nerves will improve blood pressure and cardiovascular parameters. Male and female Sprague Dawley rats were instrumented with hemodynamic transmitters for telemetry. After a baseline period on 20% glucose+0.4% NaCl diet, rats were assigned to the following groups: 20% glucose+0.4% NaCl treated with sham (G-Sham) or 20% fructose+4% NaCl with either sham (F-Sham), afferent nerve denervation (A-RDNx), or total renal nerve denervation (T-RDNx) for 3 weeks. Mean arterial pressure (MAP) was 110.3 ±1.9 mmHg in G-Sham but was elevated in the F-Sham and A-RDNx male rats, 119.9 ± 2.6 mmHg (p<0.05) and 124±5.0 (p<0.01) mmHg respectively. T-RDNx male group displayed MAP similar G-Sham rats: 114±1.29 mmHg. MAP was similar in all groups of female rats, G-Sham, F-Sham, A-RDNx, and T-RDNx: 108.3±0.1., 110.3±1.8, 110.4±0.2, and 109.0±0.6 mmHg, respectively. Pulse wave velocity (PWV) of the thoracic aorta was elevated in male F-Sham (514±58 mm/s) compared with G-sham rats (351±25 mm/s). Neither A-RDNx (550±42) nor T-RDNx (431±69 mm/s) improved PWV. In female rats, PWV did not differ among the groups: G-Sham (396 ± 46 mm/s), F-Sham (409 ±63mm/s), A-RDNx (445±48 mm/s) and T-RDNx (391±42 mm/s). Ex vivo myography was performed on thoracic aorta rings in response to phenylephrine (PE), acetylcholine (ACh) or sodium nitroprusside (SNP). Constriction with PE was greatest in both male and female F-Sham rats compared with G-Sham, A-RDNx, and T-RDNx rats. Vasodilation to ACh was similar among all the groups in both sexes; however, vasodilation to SNP was significantly attenuated only in male F-Sham vs G-Sham rats. A-RDNx and T-TDNx did not alter the response to SNP in fructose-fed rats. Left ventricular mass was no different among the groups in both male and female rats, but fibrosis was greater in both male and female F-Sham vs all other groups. Combined fructose and high salt diet increased blood pressure and PWV in male but not female rats. Vascular constriction in response to adrenergic stimulation was augmented in both sexes but endothelium-independent dilation was diminished in only in males. Left ventricular mass did not differ but cardiac fibrosis was increased in both male and female rats. Funded by NIH grant HL163844 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.