Cardiovascular responses evoked by carbachol microinjection into the posterior hypothalamus involves ganglionic nicotinic and muscarinic mechanisms.
1. Microinjection of the cholinergic agonist carbachol (3.3, 5.5 and 13.2 nmol) into the posterior hypothalamic nucleus of conscious rats evokes a dose-dependent increase in blood pressure. The pressor response evoked by the lower doses of carbachol was attenuated by pretreatment with the ganglionic nicotinic receptor antagonist pentolinium (10 mg kg(-1), i.v.) while blockade of V1-vasopressin receptors with [d(CH2)5Tyr(Me)]AVP (20 microg kg(-1), i.v.) reduced the pressor response evoked by the highest dose. 2. The combination of pentolinium and the muscarinic receptor antagonist methylatropine (2 mg kg(-1), i.v.) completely blocked the response evoked by the lower doses while the addition of [d(CH2)5Tyr(Me)]AVP to these two antagonists was required for further inhibition of the pressor response to the highest dose of carbachol. Bilateral adrenal demedullation did not affect the pressor response evoked by 5.5 or 13.2 nmol of carbachol. 3. Treatment of intact and adrenal demedullated rats with pentolinium after the pressor response to 13.2 nmol of carbachol was underway reversed the pressor response, but not to the same degree as that provided by the combination of pentolinium and methylatropine, or pentolinium and [d(CH2)5Tyr(Me)]AVP. 4. Methylatropine or [d(CH2)5Tyr(Me)]AVP caused a slight reversal of the carbachol-induced pressor response once it was underway in intact rats. Methylatropine given before or after pentolinium worked with the pentolinium to completely reverse the response. Methylatropine given alone reversed the bradycardia evoked by carbachol to a tachycardia which itself was antagonized by subsequent treatment with pentolinium. 5. These results suggest that the pressor response evoked by carbachol microinjection into the posterior hypothalamic nucleus of conscious rats involves sympathoexcitation and vasopressin release. The sympathoexcitation involves nicotinic and muscarinic receptors in autonomic ganglia.
Methvin
J M
JM
Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501, USA.
Martin
J R
JR
D000313:Adrenal Medulla / Q000601:surgery; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008845:Microinjections; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology; D010425:Pentolinium Tartrate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D065092:Antidiuretic Hormone Receptor Antagonists; D001286:Atropine Derivatives; D005730:Ganglionic Blockers; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D010276:Parasympatholytics; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; C006649:methylatropine; D002217:Carbachol; D010425:Pentolinium Tartrate