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INCREASED CARDIAC SYMPATHETIC DRIVE AND REDUCED VAGAL MODULATION FOLLOWING ENDOTHELIN RECEPTOR ANTAGONISM IN HEALTHY CONSCIOUS RATS
Author(s) -
Souza Hugo CD,
Terzini Geisa CSV,
Da Silva Valdo JD,
MartinsPinge Marli C,
Salgado Helio C,
Salgado MariaCristina O
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.04866.x
Subject(s) - bosentan , baroreflex , endothelin receptor , medicine , heart rate , endocrinology , blood pressure , autonomic nervous system , tachycardia , propranolol , anesthesia , cardiology , receptor
SUMMARY1 The present study evaluated changes in autonomic control of the cardiovascular system in conscious rats following blockade of endothelin (ET) receptors with bosentan. 2 Rats were treated with bosentan or vehicle (5% gum arabic) for 7 days by gavage. 3 Baseline heart rate (HR) was higher in the bosentan‐treated group compared with the control group (418 ± 5 vs 357 ± 4 b.p.m., respectively; P < 0.001). This baseline tachycardia was associated with a lower baroreflex sensitivity of the bradycardiac and tachycardiac responses in the bosentan‐treated group compared with the control group. Sequential blockade of the parasympathetic and sympathetic autonomic nervous system with methylatropine and propranolol showed a higher intrinsic HR in the bosentan‐treated group compared with the control group (411 ± 5 vs 381 ± 4 b.p.m., respectively; P < 0.05). This was accompanied by a higher cardiac sympathetic tone (31 ± 1 vs 13 ± 1%, respectively; P < 0.01) and a lower vagal parasympathetic tone (69 ± 2 vs 87 ± 2%, respectively; P < 0.01) in the bosentan‐treated group compared with the control group. Variance and high‐frequency oscillations of pulse interval (PI) variability in absolute and normalized units were lower in the bosentan‐treated group than in the control group. Conversely, low‐frequency (LF) oscillations of PI variability in absolute and normalized units, as well as variance and LF oscillations of systolic arterial pressure variability, were greater in the bosentan‐treated group than the control group. 4 Overall, the data indicate an increased cardiac sympathetic drive, as well as lower vagal parasympathetic activity and baroreflex sensitivity, in conscious rats after chronic blockade of ET receptors with bosentan.