Mechanism of Suppression of Vasopressin during Alpha-Adrenergic Stimulation with Norepinephrine

Abstract

A B S T R A C T Recent studies have demonstrated that the water diuresis associated with intravenous infusion of norepinephrine is mediated primarly by suppression of antidiuretic hormone (ADH) release. To investigate whether the increase in cerebral perfusion pressure with intravenous norepinephrine (0.5 jg/kg/min) is directly responsible for suppression of ADH release, the carotid circulation of dogs was pump-perfused bilaterally to selectively increase cerebral perfusion pressure. In six experiments cerebral perfusion pressure was increased from a mean of 125 to 151 mm Hg and then returned to 120 mm Hg. This maneuver was not associated with a reversible increase in renal water excretion. The possibility was also examined that norepinephrine exerts a direct central effect to suppress ADH release. In 12 experiments norepinephrine was infused into the carotid artery in a subpressor dose (0.12 ,tg/kg/min) estimated to equal the amount of the catecholamine reaching the cerebral circulation with intravenous norepinephrine. The urinary osmolality (Uosm) was not significantly altered with intracarotid norepinephrine (932 to 959 mosmol/kg H20. The possibility was also examined that changes in autonomic neural tone from arterial baroreceptors is responsible for suppression of ADH release with intravenous norepinephrine. In sham-operated animals intravenous norepinephrine diminished Uosm from 1,034 to 205 mosmol/kg H20 (P < 0.001) whereas in animals with denervated arterial baroreceptors intravenous norepinephrine was not associated with a significant alteration in Uosm (1,233 to 1,232 mosmol/kg) H20. These different effects on urinary osmolality occurred in the absence of differences in plasma osmolality and volume status. The results therefore indicate that norepinephrine primarily suppresses ADH release by altering autonomic baroreceptor tone rather than by a diReceived for publication 9 July 1973 and in revised form 29 August 1973. rect central or pressor effect of the catecholamine. This same mechanism may be the primary pathway for other nonosmotic influences on ADH release. INTRODUCTIONThe effect of intravenous norepinephrine to increase renal water excretion has been well documented in both humans (1-3) and animals (4, 5). Recent experimental evidence has demonstrated that this effect of norepinephrine is primarily related to its alpha adrenergic-stimulating properties (4,5). Moreover, studies from our laboratory have shown that this effect of norepinephrine on -renal water excretion is mediated primarily by suppression of vasopressin release rather than a direct effect

Conditions for secretion of vasopressin in pressor amounts in water-replete rats.

“…However, the latter authors further ascribed this effect of noradrenaline to altering autonomic baroreceptor tone (BERL et a!.,1974). This cannot be the major cause of the inhibition of vasopressin secretion in pressor amounts by noradrenaline in the rat, because it was still present after sinoaortic denervation.…”

Role of Plasma Vasopressin in Impaired Water Excretion of Glucocorticoid Deficiency

“…In addition to nicotine (25), these stimuli include systemic alpha (30) and beta (31) adrenergic stimulation, acute constriction of the thoracic inferior vena cava (32), left atrial distention (33), atrial tachycardia (34), and hypoxia (35). From these results has emerged the hypothesis that the nonosmotic release of vasopressin may have evolved as an integral part of the alarm reaction (36).…”

Mechanism of Effect of Hypoxia on Renal Water Excretion

“…Food was withheld 18 h before the experiment and all animals had free access to water. The animals were anesthetized with intravenous pentobarbital (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) mg/kg), intubated, and ventilated with room air with a Harvard respirator (Harvard Apparatus Co., Inc., Millis, Mass.). Ventilator tidal volume was set at 15-20 ml/kg body weight, and ventilator rate was adjusted to maintain normal alveolar ventilation (Pco2 of 25-35 mm Hg).…”

“…On the morning of the experiment, baroreceptor denervation and bilateral cervical vagotomy were carried out as previously described (27). In these animals, completeness of baroreceptor denervation was assessed by abolition of the pressor response to occlusion of each common carotid artery below the level of the carotid sinus that was present before denervation.…”