Central Rho kinase inhibition improves baroreflex gain and cardiac autonomic balance in conscious rabbits with CHF

Abstract

Recent data from our lab have shown that central Rho kinase (ROCK) inhibition normalizes disturbances in baroreflex (BR) function and cardiac sympathovagal balance induced by chronic heart failure (CHF). We hypothesized that non‐invasive measures would similarly reflect the autonomic benefits of central ROCK inhibition. Rabbits were either paced into CHF or unpaced (Sham). Intracerebroventricular infusion of either the ROCK inhibitor Fasudil (Fas; 25 ng/kg/min) or vehicle was initiated. Spontaneous BR sensitivity, pulse rate variability standard deviation of normal‐to‐normal intervals (PRV), and pulse rate variability low‐frequency/high‐frequency power spectral density (PRV LF/HF PSD) were computed from steady state parameters of animals in four treatment groups (Sham Veh, Sham Fas, CHF Veh, CHF Fas). BR sensitivity was decreased in CHF Veh rabbits compared to Sham Veh (15.9 ± 1.9 ms/mmHg vs. 4.5 ± 1.3 ms/mmHg, p < .001) while Fas tended to improve BR sensitivity in CHF animals (9.5 ± 1.3 ms/mmHg). CHF Veh rabbits had decreased PRV compared to Sham Veh (12.6 ± 1.0 ms vs. 38.0 ± 2.4 ms, p < .001) which tended to be restored in CHF Fas animals (18.6 ± 1.3 ms). The increased PRV LF/HF PSD in CHF Veh relative to Sham Veh rabbits (1.41 ± .18 vs. 0.53 ± .13, p < .001) tended to be attenuated in CHF Fas rabbits (0.73 ± 0.21). These data provide further evidence that central ROCK inhibition restores autonomic function and balance in CHF.