Acetylcholine produces cerebrovascular constriction through activation of muscarinic-1 receptors in the newborn pig.
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), an M-1 agonist, produced pial arteriolar constriction (diameters were 140 +/- 8, 127 +/- 9 and 111 +/- 8 microns 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 microns 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 F1 alpha, prostaglandin E2, thromboxane B2 and prostaglandin F2 alpha. 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.
Armstead
W M
WM
Department of Physiology and Biophysics, University of Tennessee, Memphis.
Mirro
R
R
Leffler
C W
CW
Busija
D W
DW
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D001626:Bethanechol Compounds; D011453:Prostaglandins; D011976:Receptors, Muscarinic; D018723:Bethanechol; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D000109:Acetylcholine