It was recently developed a transgenic animal model with overexpression of cholinergic neurotransmission. This mouse, named ChAT-ChR2-EYFP, has several extra copies of the vesicular acetylcholine transporter (VAChT) gene and exhibits three-fold increase in the release of acetylcholine. However, the consequences of overexpression of VAChT protein to the cardiovascular system have not yet been characterized. Therefore, we have investigated the effects of the overexpression of the gene of VAChT on arterial pressure (AP) and heart rate (HR) as well as the autonomic cardiovascular regulation. Mice were assigned into two groups: Wild-type (WT, n=7) and ChAT-ChR2-EYFP (n=7). These animals were anesthetized (isoflurane) and implanted with probes to record AP by telemetry. After 10 days, the mice had basal AP and HR recorded continuously. Assessment of the autonomic function was conducted throughout the following approaches: 1) cardiac sympathovagal balance evaluated by HR responses to methylatropine and propranolol; 2) overall HR variability; 3) spontaneous baroreflex sensitivity by the sequence analysis. ChAT-ChR2-EYFP mice showed lower basal HR (461±8 vs. 502±14 bpm, p<0.01) but similar AP as compared to WT mice. ChAT-ChR2-EYFP mice exhibited higher vagal tone (Δbpm, 169±14 vs. 117±6, p=0.03) and lower HR after double autonomic blockade (IHR, 456±8 vs. 509±11 bpm, p<0.001). HR variability was similar between groups (SDNN: 88±16 vs. 65±7 ms; RMSSD: 11.4±1 vs. 9.7±0.5 ms). However, the baroreflex sensitivity (7.5±1.5 vs. 4.1±0.5 ms/mmHg, p=0.05) was higher in ChAT-ChR2-EYFP mice. Altogether, the results show that the cardiovascular autonomic regulation of ChAT-ChR2-EYFP mice is characterized by higher parasympathetic tone, combined with a lower basal HR and IHR. Moreover, these mice present greater baroreflex sensitivity.
Simulation of autonomic blockade in mathematical model of cardiovascular regulation
