Depressed baroreflex in heart failure is not due to structural change in carotid sinus nerve fibers

Abstract

It is well known that the baroreceptor reflex is blunted in the heart failure state. However, the mechanisms for this depression are not well understood. The aim of the present study was to determine if carotid sinus nerve fiber density is decreased in the heart failure state. Experiments were carried out in pacing-induced heart failure and normal dogs. The carotid sinus nerve (CSN) was dissected and the CSN discharge responses to changes in arterial pressure with nitroglycerin (25 μg/kg, i.v.) or phenylephrine (10 μg/kg, i.v.) were recorded. Thereafter, the carotid sinus area was isolated and perfused with oxygenated Krebs-Henseleit solution. Carotid sinus baroreceptor single-unit activity was recorded and a carotid sinus pressure-discharge curve was constructed using either static or pulsatile pressure. Finally, the carotid sinus nerve was removed and fixed at its in situ length in 3% glutaraldehyde. The fixed carotid sinus nerve was cut transversely in 0.5–1.0-μm sections and prepared for electron microscopy. A photographic collage of the CSN was then analyzed at 4000 × magnification. The total number, diameter and area of myelinated and non-myelinated fibers were measured with a digitizer and the density and diameter distribution were calculated. Carotid sinus nerve discharge responses to change in arterial pressure were significantly blunted in dogs with pacing-induced heart failure. Furthermore, single-unit baroreceptor responses to both static and pulsatile pressurization were markedly depressed in dogs with heart failure. However, there was no change in either fiber density or the ratio of myelinated fibers to unmyelinated fibers in the carotid sinus nerve in heart failure. In addition, there was no change in the distribution of either fiber diameter or cross-sectional area in the carotid sinus nerve in dogs with heart failure. These data indicate that there is no significant change in the number or type of fibers in the CSN of dogs with heart failure. Therefore, the depressed baroreceptor reflex in heart failure is not due to structural changes in fibers of the CSN. The depressed baroreflex is most likely due to desensitization of individual baroreceptors.