Diminazene Aceturate Improves Autonomic Modulation in Pulmonary Hypertension

Abstract

Our studies have demonstrated that diminazene aceturate (DIZE) protects rats from monocrotaline (MCT)-induced pulmonary hypertension (PH). The present study was conducted to determine if these effects of DIZE are associated with improvements in autonomic nervous system (ANS) modulation. A single dose of MCT (50mg/kg) was subcutaneously injected to induce PH. A subset of MCT rats were treated with DIZE (15mg/kg/day) for 21 days. ANS control was evaluated by spectral and symbolic analysis of heart rate variability (HRV). MCT induced a significant (p<0.001) increase in right ventricular systolic pressure (62±14mmHg) when compared to all other groups (Control: 26±6; DIZE alone: 29±5; MCT+DIZE: 31±7). MCT treatment was associated with a significant decrease in HRV versus control (s2; Control: 93±32; DIZE: 64±58; MCT+DIZE: 41±15 and MCT: 14±11) and with an increase in the cardiac sympathetic modulation, observed by 0V pattern of symbolic analysis (Control: 4±1; DIZE: 8.8±6.1; MCT+DIZE: 2.9±2.4 and MCT: 11±6.3). This observation was confirmed by the LF/HF index of spectral analysis (Control: 0.4±0.09; DIZE: 0.06±0.007; MCT+DIZE: 0.14±0.1and MCT: 1.0±0.7) which showed that DIZE was able to recover the ANS balance. Thus, our results demonstrate that MCT-induced PH is associated with a significant increase in sympathetic modulation and a decrease in HRV. Furthermore, DIZE was able to reestablish the ANS balance.