Proceedings of The Physiological Society

Kings College London (2005) J Physiol 565P, C176


Baroreceptor dysfunction induced by hypercholesteremia in the guinea pig

Graves, Jonathan Edward; Owen, Joy ; Lewis, Stephen ;

1. Dept Physiology & Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.

We have recently demonstrated that dietary-induced hypercholesteremia causes cardiac concentric remodeling in the guinea pig. The autonomic nervous system has been implicated in mediating changes in cardiac size and geometry and is likely to play a role in the expression of this remodeling. The purpose of this study was to determine whether the baroreceptor reflex control of cardiac sympathetic and parasympathetic nerve activity was disturbed in cholesterol-fed guinea pigs. Groups of guinea pigs were fed certified guinea pig chow with or without 1% cholesterol for 13 weeks (n = 4 per group). The guinea pigs were anesthetized with ketamine (120 mg/kg ip)-acepromazine (12 mg/kg ip) and a catheter was placed in a jugular vein to administer drugs and into a carotid artery to determine pulsatile (PAP) and mean (MAP) arterial blood pressures and heart rate. The guinea pigs were allowed at least 4 days to recover from surgery. The guinea pigs received bolus doses of the alpha-1-adrenoceptor agonist, phenylephrine (1-40 mg/kg iv), to elicit pressor responses and bolus doses of the nitric oxide-donor, sodium nitroprusside (1-40 mg/kg iv), to elicit depressor responses. The maximal changes in heart rate in response to the changes in MAP were recorded and subjected to sigmoidal curve fitting analyses. Differences between means were analysed by repeated measures ANOVA Cholesterol fed guinea pigs had a similar MAP to controls (77 ± 4 vs 75 ± 4 mmHg, P 〈 0.05). Resting heart rate of cholesterol fed guinea pigs were also similar to controls (249 ± 9 vs 269 ± 13 bpm, P 〈 0.05). The sensitivity (gain, Gave) of the baroreflex was markedly diminished in cholesterol-fed as compared to control guinea pigs (2.63 ± 0.14 vs 4.08 ± 0.20 bpm/mmHg, P 〈 0.05). The heart rate range (upper plateau-lower plateau) of the baroreceptor heart rate reflex was markedly impaired in cholesterol-fed as compared to control guinea pigs (69 ± 6 vs 178 ± 11, bpm, P 〈 0.05). The maximal increases in heart rate for the cholesterol-fed and control animals were 34 ± 6 and 92 ± 10 bpm, respectively (P 〈 0.05) whereas the maximal decreases in heart rate were 35 ± 6 and 90 ± 8 bpm, respectively (P 〈 0.05). Dietary-induced hypercholesteremia causes impaired baroreceptor reflex function in the guinea pig. Further studies will address whether baroreceptor dysfunction precedes induction of cardiac concentric remodeling and plays a role in changing cardiac geometry.

Where applicable, experiments conform with Society ethical requirements