S-51-5: different contribution of afferent renal nerves to development of hypertension and hypertensive heart failure in several rat models of hypertension

Objective: Renal nerves contain efferent and afferent fibers. Acute stimulation of the afferent nerves increases central sympathetic outflow. 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. Design and method: Selective afferent renal nerve denervation (ARDN) or sham operation was performed in the following models: (1) SHRSP at 9 weeks of age; (2) 4% high-salt diet (HS)-fed SHRSP at 8 weeks (HS from 8 weeks); (3) 8% HS-fed Dahl salt-sensitive rats at 9 weeks (HS from 6 weeks); and (4) 8% HS-fed Dahl salt-sensitive rats at 9 weeks (HS from 7 weeks). Dahl rats fed 0.3% low-salt diet (LS) were used as controls for (3) and (4). Blood pressure (BP) was measured by telemetry in (1) and (2), and by tail-cuff method in (3) and (4). The experimental period ended at the following age: (1) 11 weeks; (2) 11 weeks; (3) 16 weeks (“HFrEF’’ phase); and (4) 19 weeks (“HFpEF’’ phase). Results: (1) Mean BP was significantly 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) was not different compared to sham-SHRSP at 11 weeks. (2) Mean BP was significantly increased from 8 weeks to 11 weeks in sham-HS-SHRSP (191.5 ± 8.1 vs 126.5 ± 4.0 mmHg, n = 6, p < 0.05). Mean BP in ARDN-HS-SHRSP (186.0 ± 7.1 mmHg, n = 6) did not differ from sham-HS-SHRSP at 11 weeks. (3) Systolic BP was significantly increased (243.6 ± 7.0 vs 140.0 ± 2.7 mmHg, n = 9 each, p < 0.05) and echocardiographic left ventricular fractional shortening (LVFS) was significantly decreased (25.9 ± 1.7 vs 48.8 ± 0.4 %, p < 0.05) in sham-HS-Dahl rats compared to LS-Dahl rats at 16 weeks. Compared to sham-HS-Dahl rats, systolic BP was not different (223.4 ± 5.5 mmHg, n = 7); however, the decreased LVFS was significantly attenuated (42.2 ± 1.2 %, p < 0.05) in ARDN-HS-Dahl rats. (4) Systolic BP was significantly increased in sham-HS-Dahl rats compared to LS-Dahl rats at 19 weeks (207.8 ± 4.5 vs 135.7 ± 3.2 mmHg, n = 8 and 6, p < 0.05), and this increase was not affected in ARDN-HS-Dahl rats (220.7 ± 2.9 mmHg, n = 7). By echocardiography, LVFS did not differ between the three groups, whereas E/e’ ratio was significantly increased in sham-HS-Dahl rats compared to LS-Dahl rats and was attenuated in ARDN-HS-Dahl rats. Conclusion: The signals from afferent renal nerves contribute to the development of HFrEF and HFpEF without affecting BP in Dahl salt-sensitive hypertensive rats, but not of hypertension in SHRSP and HS-fed SHRSP.