P180 CONTRIBUTION OF AFFERENT RENAL NERVES TO HYPERTENSION AND HYPERTENSIVE HEART FAILURE

Background and Objective: Renal nerves contain efferent and afferent fibers. This study aimed to investigate the contribution of afferent renal nerves to the development of hypertension and hypertensive heart failure in several rat models of hypertension. Methods: Selective afferent renal nerve denervation (ARDN) or sham operation was performed in the following models: (1) SHRSP at 9 weeks; (2) 4% high-salt diet (HS)-fed SHRSP at 8 weeks (HS from 8 weeks); and (3) 8% HS-fed Dahl salt-sensitive rats at 9 weeks (HS from 6 weeks). Dahl rats fed 0.3% low-salt diet were controls for (3). Blood pressure (BP) was measured by telemetry in (1) and (2), and by tail-cuff method in (3). Results: (1) Mean BP was elevated from 9 weeks to 11 weeks in sham-SHRSP (155.2±2.0 vs 144.0±1.9 mmHg, n=10, p<0.05). Mean BP in ARDN-SHRSP (157.8±2.7 mmHg, n=10) did not differ from sham-SHRSP at 11 weeks. (2) Mean BP increased from 8 weeks to 11 weeks in HS-sham-SHRSP (191.5±8.1 vs 126.5±4.0 mmHg, n=6, p<0.05). Mean BP in HS-ARDN-SHRSP (186.0±7.1 mmHg, n=6) did not differ from HS-sham-SHRSP at 11 weeks. (3) Systolic BP increased (243.6±7.0 vs 140.0±2.7 mmHg, n=9 each, p<0.05) and echocardiographic left ventricular (LV) fractional shortening decreased (25.9±1.7 vs 48.8±0.4%, p<0.05) in HS-sham-Dahl rats compared to low-salt controls at 16 weeks (“HFrEF” phase). LV weight, lung weight, and LV fibrosis were significantly increased in HS-sham-Dahl rats compared to controls. ARDN attenuated these changes except for BP. At 12 weeks (pre-HFrEF phase), plasma norepinephrine levels increased in HS-sham-Dahl rats compared to controls and were attenuated by ARDN (controls 188.7±16.5, HS-sham 563.8±82.7, HS-ARDN 327.4±50.2 pg/ml; n=15, 12, 14; p<0.05). Conclusions: Signals from afferent renal nerves contribute to sympathoexcitation and the development of HFrEF without affecting BP in Dahl salt-sensitive hypertensive rats, but not to the development of hypertension in SHRSP and HS-fed SHRSP.