Acetylcholine produces cerebrovascular constriction through activation of muscarinic-1 receptors in the newborn pig

W. M. Armstead, R. Mirro, Charles Leffler, D. W. Busija

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19 Citations (Scopus)

Abstract

This study was designed to characterize the nature of responses to selective muscarinic (M)-1 and M-2 agonists and to determine the receptor subtype which mediates the vascular response to acetylcholine in the cerebral circulation of the newborn pig. Pial arterioles of anesthetized newborn pigs were observed using the closed cranial window method. Topical McN-A-343 (10-7, 10-4 M), and M-1 agonist, produced pial arteriolar constriction (diameters were 140 ± 8, 127 ± 9 and 111 ± 8 μm for control, 10-7 and 10-4 M McN-A-343) that was blocked by topical pirenzepine (10-3 M), an M-1 antagonist. Topical bethanachol (10-7, 10-4 M), an M-2 agonist, produced pial arteriolar dilation (diameters were 148 ± 8, 169 ± 10 and 181 ± 10 μm for control, 10-7 and 10-4 M bethanachol) that was blocked by 4-DAMP 4-diphenylacetoxy-N'-methylpiperidine methiodide (10-3 M), an M-2 antagonist. Responses to MCN-A-343 were unchanged after 4-DAMP, and responses to bethanachol were unchanged after pirenzepine. Topical McN-A-343 and bethanachol elicited modest increases in cortical periarachnoid cerebrospinal fluid levels of 6-keto-prostaglandin F(1α), prostaglandin E2, thromboxane B2 and prostaglandin F(2α). Topical acetylcholine (10-7, 10-4 M) elicited pial arteriolar constriction and large increases in cerebrospinal fluid prostanoid levels which were blocked by atropine (0.5 mg/kg i.v.) and topical pirenzepine (10-3 M), but not by topical 4-DAMP. These data demonstrate the existence of M-1 and M-2 receptors in the cerebral circulation of the newborn pig and indicate that acetylcholine elicits cerebrovascular constriction and increased cerebrospinal fluid prostanoid synthesis via activation of M-1 receptors.

Original languageEnglish (US)
Pages (from-to)926-933
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume247
Issue number3
StatePublished - 1988

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(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
Muscarinic Receptors
Pirenzepine
Constriction
Acetylcholine
Cerebrovascular Circulation
Swine
Cerebrospinal Fluid
Prostaglandins F
Prostaglandins
Thromboxane B2
Arterioles
Atropine
Dinoprostone
Cholinergic Agents
Blood Vessels
Dilatation
4-diphenylacetoxy-1,1-dimethylpiperidinium

All Science Journal Classification (ASJC) codes

  • Pharmacology

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Acetylcholine produces cerebrovascular constriction through activation of muscarinic-1 receptors in the newborn pig. / Armstead, W. M.; Mirro, R.; Leffler, Charles; Busija, D. W.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 247, No. 3, 1988, p. 926-933.

Research output: Contribution to journalArticle

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