In both fetal and adult animals, hemorrhage initiates a set of physiological responses which act in concert to return blood volume and pressure to prehemorrhage levels. Hypothetically, these responses are initiated by changes in afferent neural activity of cardiovascular mechanoreceptors, which respond to changes in vessel wall diameter or cardiac chamber size. At the present time, little is known about the localizations of these receptors in the sheep circulation, whether they function in fetal life, or whether the responses to hemorrhage change throughout development. Accordingly, the experiments proposed in this application will employ chronically-catheterized fetal sheep to identify locations of cardiovascular receptors responsible for controlling hormonal responses to hemorrhage. Fetal sheep will be prepared with balloon-tipped Swan-Ganz catheter in the inferior and superior vena cana and with an extravascular balloon around the ascending aorta and pulmonary artery in order to produce controlled reductions in pressures in the arterial system and within the chambers of the heart. These balloons will also be used to alter intracardiac and arterial pressures relative to each other. By quantitating renin, ACTH, cortisol, and vasopressin responses to alterations in arterial and intracardiac pressures in intact fetuses and in fetuses which had been subjected to selective denervations of arterial and intracardiac mechanoreceptors, it will be possible to identify anatomical areas containing hormone-controlling mechanoreceptors. In addition to denervation experiments designed to locate receptors, the role of Angiotensin II in the control of ACTH and vasopressin responses to hypotension will be assessed. To date, these basic questions concerning the neural mediators of hormonal responses to hemorrhage have not been addressed. Therefore, the results of these experiments will define the mechanisms of the fetal hormonal response to hemorrhagic stress.
Wood, Charles E (2002) The ovine fetal endocrine reflex responses to haemorrhage are not mediated by cardiac nerves. J Physiol 541:613-22 |
Chen, H G; Wood, C E (1992) Reflex control of fetal arterial pressure and hormonal responses to slow hemorrhage. Am J Physiol 262:H225-33 |
Papanek, P E; Wood, C E; Fregly, M J (1991) Role of the sympathetic nervous system in cold-induced hypertension in rats. J Appl Physiol 71:300-6 |
Wood, C E; Chen, H G; Bell, M E (1989) Role of vagosympathetic fibers in the control of adrenocorticotropic hormone, vasopressin, and renin responses to hemorrhage in fetal sheep. Circ Res 64:515-23 |
Wood, C E (1989) Sinoaortic denervation attenuates the reflex responses to hypotension in fetal sheep. Am J Physiol 256:R1103-10 |