Mechanisms underlying the pressor responses to acute and chronic intraventricular administration of carbachol in the rat.
Infusions of carbachol into the posterior region of the 3rd ventricle of rats for 7 days produced a sustained elevation of blood pressure and heart rate at doses of 0.6 and 1.2 microgram/hr, but only transient rises in blood pressure were obtained at 2.4 microgram/hr. Carbachol, at 0.6 microgram/hr, increased water consumption. At 1.2 microgram/hr, the dipsogenic effect was observed in 50% of the animals and at 2.4 microgram/hr there was no significant change in drinking. Plasma vasopressin levels, measured by radioimmunoassay, were increased by 19-fold 3 min after acute i.c.v. administration of carbachol (0.5 microgram/rat). However, in rats infused with carbachol for 2 or 5 days, the vasopressin levels were not significantly different from controls. The pressor responses to acute and chronic administration of carbachol could be ascribed to the stimulation of periventricular muscarinic receptors because the effects were blocked by atropine, but not by hexamethonium. In carbachol-infused animals, the pressor responsiveness to i.v. norepinephrine and vasopressin were unchanged. From studies using phentolamine, chlorisondamine and a specific vasopressin vasopressor antagonist, it could be inferred that the pressor responses to acute i.c.v. injections of carbachol were due to increased sympathetic activity and vasopressin release. However, the sustained hypertension produced by chronic infusion of carbachol was due primarily to increased sympathetic activity and not to increased plasma levels of vasopressin.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D007276:Injections, Intraventricular; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014667:Vasopressins / Q000097:blood
D011976:Receptors, Muscarinic; D014667:Vasopressins; D002217:Carbachol