Central cholinergic mechanisms mediate swallowing, renal excretion, and c-fos expression in the ovine fetus near term

Abstract

mechanisms mediate swallowing, renal excretion, and c-fos expression in the ovine fetus near term. Am J Physiol Regul Integr Comp Physiol 296: R318 -R325, 2009. First published September 10, 2008 doi:10.1152/ajpregu.90632.2008.-Fetal swallowing and renal metabolism contribute importantly to amniotic and body fluid homeostasis. To determine central cholinergic modulation of swallowing activity and renal excretion associated with neural activity, we examined the effects of intracerebroventricular injection of carbachol, a cholinergic agonist, in ovine fetuses at 0.9 gestation. Fetuses were chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyogram electrodes, as well as lateral ventricle and vascular catheters. Electrodes were also implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, and urine output were monitored during basal period and the experimental period following intracerebroventricular injection of 0.9% NaCl as the control (n ϭ 5) or carbachol (3 g/kg, n ϭ 5). Central carbachol did not significantly change fetal low voltage (LV) and high voltage (HV) ECoG temporal distributions. However, swallowing activity during LV ECoG was elevated significantly after intracerebroventricular carbachol. Associated with the swallowing activation, c-fos immunoreactivity in the putative dipsogenic center, subfornical organ, was enhanced significantly. The fetal urine flow rate and renal Na ϩ , K ϩ , and Cl Ϫ excretion were markedly increased following intracerebroventricular carbachol and sustained at the high level for at least 2 h. The results indicate that the central cholinergic mechanism is established and functional in regulation of fetal behavior and renal excretion at least at 0.9 gestation, which plays an important role in maintenance of fetal body fluid homeostasis.fetus; carbachol; thirst STIMULATED WATER INTAKE, IN concert with renal water and electrolyte excretion, is the fundamental physiological mechanism that maintains body fluid homeostasis. It is well established that in adult animals, central cholinergic mechanisms play an important role in the control of cardiovascular and body fluid homeostasis (12,15). Central application of cholinergic agonist, carbachol, elicits a variety of physiological responses, including natriuetic, dipsogenic, and pressor responses, as well as vasopressin secretion (2,23,44). Our recent studies demonstrated that intracerebroventricular injection of carbachol also produced pressor responses (42) in the ovine fetus near term, indicating that the central cholinergic mechanism-mediated cardiovascular regulation is functional before birth. However, the role of central cholinergic mechanisms in fetal fluid balance and renal excretion is largely unknown.Progress has been made in demonstrating that swallowing activity can be regulated by hyperosmotic, hypovolemic, and other stimuli such as ANG II and neuropeptide Y in late gestation (31,33,48,49). Fetal renal flu...

Angiotensin-converting enzymes and drug discovery in cardiovascular diseases

“…In recent studies, we investigated the functional development of brain ACE related to the cardiovascular regulation in utero in the chronically prepared near-term ovine fetus with intracerebroventricular injection of Ang I. An in utero survival surgery was exerted in the ovine fetuses [97,98]. An intracranial cannulae was placed in the fetal lateral ventricle at 70%-90% gestation.…”