title: Endothelium-derived relaxing factor inhibits constrictor responses of large cerebral arteries to serotonin.
abstract: Endothelium-derived relaxing factor [EDRF, nitric oxide (NO) or a NO-containing compound] influences basal tone of cerebral blood vessels and mediates vasodilation in response to several stimuli. It is not known whether EDRF also modulates responses to cerebral vasoconstrictor stimuli in vivo. Our goal was to determine whether formation of EDRF inhibits constrictor responses of large cerebral arteries to serotonin. We measured cerebral blood flow (microspheres) and pial microvascular pressure (servo null) in anesthetized rabbits and calculated resistance of large cerebral arteries. Responses to an inhibitor of NO formation, NG-nitro-L-arginine (L-NNA, 3 mg/kg i.v.), were examined. L-NNA produced an increase in resistance of large arteries and total cerebral vascular resistance of approximately 15% (p less than 0.05 for both variables) and a small decrease in cerebral blood flow (35 +/- 9 vs. 32 +/- 7 ml min-1 100 g-1, mean +/- SD, p less than 0.05). Under control conditions, infusion of serotonin (10 micrograms kg-1 min-1, into the left atrium) produced an increase in resistance of large arteries. Following treatment with L-NNA, the change in resistance of large arteries in response to serotonin was increased more than twofold (0.20 +/- 0.17 vs. 0.43 +/- 0.21 mm Hg ml-1 min 100 g, p less than 0.05). In contrast, L-NNA did not alter the increase in resistance of large arteries during hypocapnia. L-arginine inhibited the effects of L-NNA on baseline cerebral vascular resistance and on responses of large arteries to serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: F M
authors.initials: FM
authors.lastname: Faraci
authors.forename: D D
authors.initials: DD
authors.lastname: Heistad
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D002545:Brain Ischemia / Q000378:metabolism*; D002536:Cerebral Arteries / Q000187:drug effects*; D004195:Disease Models, Animal; D006706:Homeostasis; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019335:Nitroarginine; D011817:Rabbits; D012039:Regional Blood Flow; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D012702:Serotonin Antagonists; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine