Mechanism of histamine-induced antidiuretic response.

1. In dogs anaesthetized with alpha-chloralose, intracerebroventricular (i.c.v.) injection of histamine induced antidiuresis and increase in jugular vein blood antidiuretic hormone (ADH) level but no change in urinary electrolytes. The mechanism of the histamine-induced antidiuretic response was analysed by the use of pharmacological agents.2. Histamine (i.c.v.) in 1-20 mug doses produced a variable effect on urine outflow as well as on the blood ADH concentration; however, higher doses (25-500 mug) of histamine elicited a dose-dependent antidiuretic response with concomitant rise in blood ADH titre.3. Repeated administration of high doses of i.c.v. histamine (400 mug) elicited a diminishing antidiuretic response which was not observable after the fourth dose, thus exhibiting tachyphylaxis. The antidiuretic response to histamine could be restored by central administration of noradrenaline (500 mug).4. Central pretreatment with mepyramine (5 mg) prevented the histamine-induced antidiuresis. Atropine (2 mg i.c.v.) was ineffective in blocking the antidiuretic effect of histamine. A diuretic response to histamine (400 mug i.c.v.) was obtained in phenoxybenzamine (i.c.v.) pretreated animals; this response could be blocked by i.c.v. injection of propranolol. Tetrabenazine pretreatment prevented the antidiuretic response to histamine.5. The results of the study lead us to conclude that histamine releases central catecholamines which activate the central adrenergic mechanism for the release of antidiuretic hormone.