Mechanism of vascular smooth muscle contraction by sodium fluoride in the isolated aorta of rat and rabbit
Adeagbo, A.S.; Triggle, C.R.
Journal of Pharmacology and Experimental Therapeutics 258(1): 66-73
1991
ISSN/ISBN: 0022-3565 PMID: 1649301 Document Number: 380610
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-tetraacetic acid Krebs' solution or nifedipine (10 .mu.M), 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 .mu.M, respectively). On the other hand, the protein kinase C antagonist staurosporine and H-7 potently (IC50 = 0.016 .+-. 0.007 and 1.1 .+-. 0.5 .mu.M, 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. F--induced contractions of aortic rings isolated from rats pretreated with pertussis toxin (50 .mu.g/kg, i.v.) were not different from rings obtained from untreated rats. We conclude that the contraction elicited by F- most likely results from an alteration in the sensitivity of the contractile proteins to low or basal levels of Cai possibly involving the activation of protein kinase C and/or the inhibition of phosphatase activity.