We have studied in conscious unrestrained rats under basal conditions the effect of activation of muscarinic and nicotinic receptors in the paraventricular nucleus on vasopressin secretion and mean arterial blood pressure. The microinjection of oxotrernorine (0.2, 2 or 20 ng), a specific muscarinic agonist, produced a substantial, dose-dependent, transient increase in the plasma vasopressin concentration. There was also a rise in mean arterial blood pressure and a bradycardia that followed the same time-course as the change in plasma vasopressin levels. The microinjection of nicotine (0.1, 1 or 10 pg) into the paraventricular nucleus had only questionable effects on vasopressin release and mean arterial blood pressure; heart rate was unaffected. These findings suggest that muscarinic receptors may be of primary importance in the paraventricular nucleus in the cholinergic stimulation of vasopressin re I ease.There is considerable evidence to suggest that central cholinergic mechanisms play a n important role in the control of vasopressin release. It has been reported that cholinergic neurons project to the paraventricular (PVN) and supraoptic nuclei (SON) (1-3). Acetylcholine and its synthetic and degradative enzymes, i.e. clioline acetyltransferase and acetylcholine esterase, have been demonstrated in the anterior hypothalamus and posterior pituitary (4-7). Receptors for acetylcholine have been demonstrated in the PVN, . Finally, the central administration of acetylcholine and its agonists (18-23) in the intact animal, and the addition of acetylcholine to the medium in which the isolated hypothalamo-neurohypophysial complex is incubated (24, 25), stimulate the release of vasopressin.It is, however, controversial whether the cholinergic receptors involved in the stimulation of vasopressin release are muscarinic 01 nicotinic. Recently, Iitake et at. (23) found that the intracerebroventricular (icv) administration of carbachol stimulated the release of vasopressin in the conscious rat and that this effect was blocked by atropine, but not by hexamethonium, suggesting that the receptors are muscarinic. These observations are in agreement with those of earlier studies in the rat (20,26), dog (18), goat (19), and sheep (22), in which antidiuresis was used as an index of vasopressin release. On the other hand, there is also evidence that activation of nicotinic receptors in the SON elicits the release of vasopressin in the rat (24, 25, 27) and cat (21, 28).In an effort to resolve the issue of the nature of the cholinergic receptors in the PVN, we have, in the present study, determined the effect on vasopressin release of the microinjection of muscarinic and nicotinic agonists into the PVN.
ResultsThe microinjection of the artificial cerebrospinal fluid (aCSF) vehicle into the PVN and the taking of blood samples were without effect on the plasma vasopressin concentration (Fig. I), mean arterial blood pressure (Fig. 2), heart rate ( Fig. 2), plasma osmolality and hematocrit. However, the microinjection of oxotremo...