Inhalation of
amyl nitrite in the water-loaded rat under
ethanol anaesthesia produced a brief fall of blood pressure followed by a prolonged antidiuretic response. The antidiuretic response to
amyl nitrite was accompanied by increased urinary excretion of
vasopressin, it was blocked by a specific
vasopressin antagonist and by a
barbiturate and it was absent in the Brattleboro rat with congenital
diabetes insipidus. These results show that the antidiuretic response to the
hypotension induced by
amyl nitrite is due to the release of
vasopressin and that this release is mediated by a neuroendocrine reflex acting through the brain stem.
Carbachol and
nicotine produced an antidiuretic response on injection into a lateral cerebral ventricle (i. vent.).
Carbachol was almost ineffective, but
nicotine much more effective, when injected into the cisterna magna (i.cist.) from which in the rat there is no access to the ventricles.
Carbachol therefore acts at a site reached from the ventricles, possibly the paraventricular nucleus.
Nicotine acts at a more distal site reached from the subarachnoid space. This site may correspond with the
nicotine-sensitive area on the ventral surface of the brain stem which has been described in the cat.
Atropine blocked the antidiuretic response to
carbachol but not that to
amyl nitrite.
Hexamethonium blocked the antidiuretic response to
amyl nitrite as well as that to
nicotine and was more effective on i.cist. than i.vent. injection. These results reveal a
cholinergic link with a nicotinic but not a
muscarinic receptor in the neural pathways controlling the release of
vasopressin in response to
hypotension. A hypothetical model is presented in which the release of
vasopressin is stimulated by a pathway arising from chemoreceptors and inhibited by a second pathway arising from stretch- and baroreceptors.
Hypotension acts by suppressing the normally predominant inhibitory pathway and stimulating the excitatory pathway.
Hexamethonium is presumed to block transmission at a synapse in the excitatory pathway at the ventral surface or, less probably, at the paraventricular and supraoptic nuclei.