Abstract 292: Cardiocirculatory Effect of the Increase of Parasympathetic Function with Pyridostigmine in Spontaneously Hypertensive Rats (SHR).
The improvement of parasympathetic function seems to be an attractive therapeutic target in hypertensive patients. The parasympathetic function can be augmented by acetylcholinesterase inhibition. We investigated the chronic effect (16 weeks) of the acetylcholinesterase inhibitor pyridostigmine (PYR) on the hemodynamics [arterial pressure (AP) and heart rate (HR)], autonomic balance (parasympathetic tone, AP and pulse interval (PI) variability), spontaneous baroreflex sensitivity and cardiac function during the development of hypertension in SHR. PYR administration (minipumps, 1.5 mg/kg/day,n=6) started with SHR aging 5 weeks. Control SHR (n=7) was implanted with empty minipump. Mean AP (MAP, mmHg) was monitored every 4 weeks, by the tail-cuff method. At the end of 16 weeks, mean femoral AP (mmHg) was recorded in conscious state and methyl atropine allowed the evaluation of the vagal tone (bpm), while the combined administration of propranolol provided the intrinsic heart rate (IHR, bpm). Cardiac function was assessed, under isofluorane anesthesia, 24h after the hemodynamic recordings. PYR reduced the MAP during the first 8 weeks only (166±6 vs 185±6 in control), while after 16 weeks PYR produced: no change in HR (334±10 vs 354±13 in control); increase in vagal tone (132±8 vs 73±9 in control) and IHR (381±8 vs 340±3 in control); reduction of AP variance (42±6 vs 71±9 in control) without change of PI variance (69±12 vs 73±9 in control); no change of spontaneous baroreflex sensitivity (1.66±0.2 vs 1.75±0.1 bpm/mmHg in control); increase of the ejection fraction (65±5 vs 46±2 % in control). Nevertheless, it was not observed significant changes in cardiac output (32±5 vs 25±3 ml/min in control), +dPdt (9731±1079 vs 8746±461 mmHg/s in control), -dPdt (-9782±1079 vs -11195±1494 mmHg/s in control) and total peripheral resistance index (1.75±0.3 vs 2.53±0.5 mmHg/ml/min in control). In conclusion, PYR reduced the MAP of the SHR only at the beginning of the treatment (8 weeks), although chronically (16 weeks) increased cardiac vagal tone and IHR while reduced the AP variability combined with an increased ejection fraction. Therefore, the increase in parasympathetic function provided only slight benefic effects during the development of hypertension in SHR.
- © 2012 by American Heart Association, Inc.