The Inability of Infusions of Angiotensin to Elevate the Plasma Vasopressin Concentration in the Anesthetized Dog

The relationship between iv infusions of angiotensin II and vasopressin release has been investigated in the anesthetized dog. In dogs sedated with morphine and anesthetized with a mixture of chloralose and urethane, a 40-min iv infusion of angiotensin II ranging from 10-60 ng/ kg/min failed to stimulate the release of vasopressin. This was observed when the control plasma levels of vasopressin were moderately elevated due to anesthesia and surgical trauma, approximately 15 M*U/ml, or when suppressed by hydration to approximately 3 nU/ml. In hydrated dogs anesthetized with pentobarbital and subjected to less surgery, the starting levels of vasopressin were 1.2 H-U/ml. In these dogs a 75-min infusion of 10 ng/kg/min of angiotensin II into a common carotid artery also failed to stimulate the release of vasopressin. {Endocrinology 90: 1647, 1972) T T HAS BEEN reported that the administra•*• tion of angiotensin directly into the ventricles of the brain in the anesthetized dog (1), the hydrated conscious goat (2), and the conscious rat (3) results in an increased release of vasopressin from the posterior pituitary. It has also been claimed that the circulating levels of vasopressin are elevated following the infusion of angiotensin II via a peripheral vein in the conscious dog (4) and a common carotid artery in the dog anesthetized with pentobarbital (1). However, the changes in the plasma vasopressin concentration in these experiments in which the angiotensin was injected into the circulation were quite small, and the results of only three experiments were reported by Mouw et al. (1). In addition, one wonders to what extent the findings in the conscious dogs (4) were influenced by emotional reactions to the experimental procedure and to the increase in blood pressure induced by the angiotensin. In view of these considerations and reports of several situations in which plasma levels of renin and vasopressin fail to change in a parallel fashion (5,6), it seemed advisable to reinvestigate the effect of the systemic infusion of angiotensin Received October 28, 1971. This work has been supported by grants HL-12990 from the National Heart Institute, USPHS, and HL-14242 (Specialized Center of Research in Hypertension). Computer assistance was supported by grant HL-09495 from the National Heart Institute, USPHS. The authors express their gratitude for the able technical assistance of Miss J. T. Crofton and Mr. S. E. Pienaar. II on the plasma concentration of vasopressin. Because of the cardiovascular effects of angiotensin, some of these studies were accompanied by measurements of arterial mean and pulse pressures and left atrial pressure, factors which play an important role in the control of vasopressin release. The infusion of angiotensin II in hydrated dogs anesthetized with either pentobarbital, or sedated with morphine and anesthetized with urethane and chloralose produced no effect on the plasma levels of vasopressin in the present investigation. Similar observations are obtained in normally hydrated dogs under morphine-urethane-chloralose anesthesia. Materials and Methods All experiments were performed on male mongrel dogs weighing 14.5-26.0 kg. Some dogs were sedated with a sc injection of 0.1 ml/kg of 2.0% morphine and anesthetized with an iv infusion of a mixture of urethane (6.0%) and chlorolose (0.6%) in 0.9% saline, approximately 9.0 ml/kg. Others were anesthetized with iv infusions of approximately 1.0 ml/ kg of 3.0% sodium pentobarbital. Surgery. The trachea and right and left femoral arteries and veins were cannulated in all dogs. In the dogs receiving morphine, urethane and chloralose anesthesia, the chest was opened in the fourth intercostal space on the left side, so that the left atrium could be catheterized via the atrial appendage. During this procedure the dog's respiration was maintained by positive pressure ventilation. The intercostal incision was then closed and a catheter was left in the pleural cavity. The chest was evacuated, arti-