Abstract 14033: Alpha2-Adrenergic Stimulation-Induced Vagal Activation is Impaired in Spontaneously Hypertensive Rats
Background: Although sympathetic overactivity is one of the major feature of spontaneously hypertensive rats (SHR), abnormality of vagal control is not fully understood compared to the sympathetic control due to the lack of good methodology to assess vagal nerve activity. High frequency components of heart rate variability are conveniently used to gain some information on vagal nerve activity, but they are inherently indirect indices. A recent application of cardiac microdialysis to the rat left ventricle to measure low levels of acetylcholine (ACh) will offer an direct assessment of vagal nerve activity to the heart in SHR.
Methods: In α-chloralose and urethane-anesthetized SHR and normotensive Wistar Kyoto (WKY) rats (n = 7 each), a microdialysis fiber (7-mm length, 310-μ m diameter, 50000 molecular weight cutoff; PAN-1200, Ashahi Chemical) was implanted into the left ventricular free wall, and was perfused with Ringer solution containing an acetylcholinesterase inhibitor eserine (100 μ M) at a rate of 1 μ l/min. After two hours of stabilization, 20-min dialysate samples were collected under baseline conditions and after intravenous administration of an α2-adrenergic agonist medetomidine (0.1 mg/kg, bolus).
Results: In WKY, medetomidine significantly decreased heart rate from 375 ± 7 to 316 ± 13 beats/min (P < 0.01) with an increase in ACh from 2.4 ± 0.6 to 4.1 ± 1.3 nM (P < 0.05). Mean arterial pressure was not changed significantly (96 ± 10 vs. 86 ± 6 mmHg). In SHR, medetomidine also decreased heart rate from 364 ± 16 to 313 ± 12 beats/min (P < 0.01) but without a significant change in ACh (2.5 ± 0.7 vs. 2.7 ± 0.7 nM). Mean arterial pressure was significantly dropped from 142 ± 13 to 67 ± 5 mmHg (P < 0.01).
Conclusion: Although an intravenous administration of an α2-adrenergic agonist medetomidine induced bradycardia in both WKY and SHR, the underlying mechanism may be different. Medetomidine decreased heart rate via vagal activation in WKY whereas it decreased heart rate mainly via sympathetic suppression in SHR. In addition to the abnormality of sympathetic control, vagal control may be impaired in SHR.
- © 2011 by American Heart Association, Inc.