title: Mechanism of vascular smooth muscle contraction by sodium fluoride in the isolated aorta of rat and rabbit.
abstract: The purpose of this study was to determine the cellular basis for fluoride ion (F-)-induced contractions of isolated aortic rings from both the rat and the rabbit. The F- contractions were not affected by endothelial denudation but were enhanced in the presence of A (0.1 or 1.0 mM) added to the bathing Krebs' solution. The contractile effect of F- also was not modified by bathing with Ca(++)-free + ethylene glycol bis(b-aminoethylether)-N,N-tetracetic acid Krebs' solution or nifedipine (10 microM), but was attenuated by inorganic (Cd++, Co++ and Ni++) Ca++ antagonists in normal and Ca(++)-free Krebs' media. Bis(o-aminophenoxy)-ethane-N-N-N'-N'-tetraacetic acid, ryanodine and intracellular Ca++ modulators, respectively, caused 36.1 +/- 6.1%, 16.4 +/- 6.8% and 52.3 +/- 7.3% inhibition of the contractile response to F- in a Ca(++)-free media while causing near complete inhibition of norepinephrine-induced contractions. F- contractions were also inhibited by the calmodulin antagonists W-7 and calmidazolium (IC50 = 23.0 +/- 7.0 and 45.0 +/- 10.0 microM, respectively). On the other hand, the protein kinase C antagonists staurosporine and H-7 potently (IC50 = 0.016 +/- 0.007 and 1.1 +/- 0.5 microM, respectively) inhibited the fluoride-induced contractions. Aortic rings from the rabbit were similarly potently antagonized by the protein kinase C inhibitors, however, K(+)-induced contractions were also equally sensitive to these agents in both rat and rabbit tissues. The putative phospholipase C inhibitor neomycin was significantly less effective (IC50 = 13.0 +/- 5.0, 0.44 +/- 0.09 and 0.89 +/- 0.40 mM) at inhibiting F- than norepinephrine and KCl contractile effects.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
authors.forename: A S
authors.initials: AS
authors.lastname: Adeagbo
authors.forename: C R
authors.initials: CR
authors.lastname: Triggle
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D004347:Drug Interactions; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology*; D019311:Staurosporine; D014661:Vasoconstriction / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D015220:Calcium Channels; D010566:Virulence Factors, Bordetella; D012969:Sodium Fluoride; D011493:Protein Kinase C; D019311:Staurosporine; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine