This study will investigate the role of neurohypophyseal vasopressin in the control of ACTH and cortisol secretion and the role of corticotropin-releasing factor (CRF) in the control of vasopressin and ACTH secretion in conscious dogs. Neurohypophysectomy attenuates the ACTH response to hypotension and attenuates the cortisol response to ovine CRF- induced increases in ACTH. The ACTH and cortisol response to nitroprusside-induced clamped decreases in blood pressure and to exogenous ovine CRF infusions will be determined in intact dogs, neurohyupophysectomized dogs with continuous vasopressin replacement, and in neurohypophsectomized dogs without vasopressin replacement (diabetes insipidus). This will determine if attenuated ACTH responses to hypotension and attenuated cortisol responses to CRF-induced increased in ACTH In neurohypophysectomized dogs can be restored to normal by alleviating the symptoms of diabetes insipidus. Acute infusions of vasopressin during hypotension in neurohypophysectomized dogs to elevate vasopressin levels observed in intact dogs will be performed to determine if the full ACTH response to hypotension requires large increases in plasma vasopressin. In addition, exogenous ACTH infusions will be used to directly assess the role of vasopressin in adrenocortical sensitivity (cortisol, aldosterone, and adrenal androgen) in conscious dogs. It has been suggested that the plasma vasopressin response to osmotic and non-osmotic stimuli are sensitive to glucocorticoid negative feedback inhibition. The glucocorticoid sensitivity of vasopressin responses to hypotension and/or hyperosmolality will be determined in conscious dogs. Dogs will be pretreated with physiological increases in plasma cortisol and the subsequent vasopressin response to nitroprusside and/or hypertonic saline will be assessed. Since the sequencing and synthesis of CRF, studies of the interaction of CRF and vasopressin have been many. The studies proposed herein will examine the role of the neurohypophysis, vasopressin, CRF, and steroid feedback in the control of the anterior and posterior pituitary and the adrenal cortex.
