Abstract 14951: Input From Renal Afferent Nerves Contributes to Hypertensive Heart Failure With Preserved Systolic Function Through Baroreflex Impairment and Sympathoexcitation

Abstract

Introduction: Activation of renal afferent nerves, which can be caused by hypertensive renal damage, increases sympathetic output. The nucleus tractus solitarius (NTS) receives the inputs from baroreflex afferent nerves as well as renal afferent nerves. Baroreflex dysfunction leads to increased left ventricular (LV) end-diastolic pressure even in the heart with preserved systolic function. The GABAergic inhibitory system in the NTS blunts the signals from baroreflex afferent nerves, resulting in increased sympathetic output. Hypothesis: Input from renal afferent nerves contributes to hypertensive heart failure with preserved systolic function through baroreflex impairment and sympathoexcitation mediated by increased GABAergic inhibition in the NTS. Methods and Results: Male Dahl salt-sensitive rats with 8% high-salt diet from 7 weeks of age develop hypertensive HFpEF at 19 weeks. These rats underwent sham surgery (Sham), selective afferent renal denervation (ARDN), or additionally dissection of baroreflex afferent nerves (ARDN+BAROX) at 9 weeks. As controls, rats underwent sham surgery with a low-salt diet. The rats were evaluated at 19 weeks. Systolic blood pressure was similarly elevated in the three groups on high-salt diet. Impaired LV diastolic function assessed by echocardiography and pressure-volume loop analysis in Sham was recovered in ARDN group, while systolic function was preserved in all the group. Decreased baroreflex sensitivity and increased sympathetic output in Sham were attenuated in ARDN group. Activity of GABAergic neurons in the NTS evaluated by immunostaining was increased in Sham compared to controls, and was attenuated in ARDN group. All of the changes in ARDN were cancelled in ARDN+BAROX group. Conclusion: Input from renal afferent nerves contributes to hypertensive heart failure with preserved systolic function through baroreflex impairment and sympathoexcitation along with increased GABAergic inhibition in the NTS.