PS-B10-4: AFFERENT RENAL NERVOUS SIGNALS CONTRIBUTE TO THE DEVELOPMENT OF HFPEF WITH SYMPATHOEXCITATION IN DAHL SALT-SENSITIVE HYPERTENSIVE RATS

Abstract

Objective: Sympathetic activation is involved in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Renal nerves contain sympathetic efferent and sensory afferent fibers. Excitation of the renal efferent nerves increases renal renin release and sodium/water retention. On the other hand, the renal afferent nerves are activated by the renal injury associated with hypertension, and acute stimulation of the afferent nerves increases sympathetic output from the brain. In this study, we investigated whether the signals from the renal afferent nerves contribute to the development of hypertensive HFpEF using a novel method of selective afferent renal nerve denervation (ARDN) in Dahl salt-sensitive rats, a widely used animal model of HFpEF. Design and method: Male Dahl salt-sensitive rats were fed 0.3% low-salt diet (LS) or 8% high-salt diet (HS) from 7 weeks of age. At 9 weeks, LS-fed rats received sham operation (LS-Sham), and HS-fed rats were randomly divided into ARDN (HS-ARDN) or sham operation (HS-Sham). At 19 weeks, blood pressure, echocardiographic parameters, organ weights, and plasma norepinephrine levels were measured, and the histological and biochemical analysis of the heart were performed. Results: Systolic blood pressure was significantly increased in HS-Sham compared to LS-Sham, and this increase was not affected in HS-ARDN. By echocardiography, left ventricular (LV) fractional shortening did not differ between the three groups; however, E/e’ ratio was significantly increased in HS-Sham compared to LS-Sham and was attenuated in HS-ARDN. LV weight / body weight ratio and lung weight / body weigh ratio were significantly increased in HS-Sham compared to LS-Sham, and were decreased in HS-ARDN. Plasma norepinephrine levels were significantly higher in HS-Sham than LS-Sham, and this increase tended to be inhibited in HS-ARDN. LV fibrosis evaluated by Masson trichrome staining was significantly increased in HS-Sham compared to LS-Sham and was attenuated in HS-ARDN. ANP mRNA expression in LV tissue was extremely increased in HS-Sham compared to LS-Sham and was significantly attenuated in HS-ARDN. Conclusion: The signals from afferent renal nerves contribute to the development of HFpEF with sympathoexcitation in Dahl salt-sensitive hypertensive rats.