Central mineralocorticoid receptor antagonism improves autonomic neural control in heart failure rats

Abstract

Heart failure (HF) is characterized by neurohumoral activation and altered autonomic cardiovascular regulation. As HF progresses there is a graded derangement of sympathovagal balance (SVB) and a reduction in rhythmical properties of sympathetic discharge. Spironolactone (Sp), a mineralocorticoid receptor (MR) antagonist, reduces mortality in HF but its effects on cardiac autonomic control are unclear. The aim of the study was to determine whether blocking central MR improves SVB in HF rats, using spectral (PSA) and symbolic (SA) analysis. Twenty-four rats underwent coronary artery ligation to induce HF (EF~35%), followed by continuous intracerebroventricular infusion of Sp or vehicle (V) for 2 or 4 weeks. Pulse interval (PI) was derived from arterial pressure recordings. In rats treated with Sp for 4 weeks compared with 2 weeks, PSA and SA revealed a significantly (∗p<0.05) greater rhythmic sympathetic component of PI (low frequency: 23.5∗ vs. 4.7 nu; 0V: 8.8∗ vs. 4%). In rats treated for 4 weeks with Sp compared with V, PSA showed enhanced vagal modulation (high frequency: 61∗ vs. 17 nu) and SA revealed a reduction in 2UV pattern (38∗ vs. 53%), a marker of short and irregular PI modulation. PSA indicates that blocking central MR improves sympathetic and parasympathetic modulation of PI in HF and SA suggests a reduction of cardiac electrical instabilities. Support: FIRST grant University of Milan NHLBI RO1 HL63915