Differential activation of rabbit femoral arteries by aluminum fluoride and sodium fluoride.
The effect of fluoride (NaF; 10 mM sodium fluoride plus deferoxamine to chelate contaminating aluminum) and fluoride plus aluminum fluorides (AlF; 10 mM sodium fluoride plus 20 microM aluminum chloride) on activation of rabbit femoral arteries was investigated. AlF and NaF produced large increases in stress (force/muscle cross-sectional area), but temporal changes were dissimilar, as were other indices of muscle activation. Stress produced by NaF developed slowly and only after a long delay of about 15 min, whereas stress produced by AlF developed rapidly after a delay of only about 5 min. NaF-induced contractions were more sustained than AlF-induced contractions. Both AlF and NaF increased the level of cross-bridge phosphorylation and the velocity of muscle shortening, but at comparable stresses, AlF produced greater increases than did NaF. AlF produced a large increase in lP production, whereas NaF produced a small increase. Also, AlF-induced stress was largely insensitive to inhibition by the calcium channel blocker, nifedipine (1 microM), whereas NaF-induced stress was largely inhibited by nifedipine. However, in tissues depleted of calcium, both agents produced potent contractions when CaCl2 was added back to the tissues (EC50 values for AlF, NaF, histamine, phenylephrine and KCl were, respectively, 0.057, 0.085, 0.11, 0.11 and 0.23 mM). AlF, but not NaF, strongly desensitized arteries to phenylephrine, causing a 73% reduction in the ability of phenylephrine to achieve maximum steady-state stress. These data suggest that fluoride contracted rabbit femoral arteries by stimulating L-type calcium channels, and that aluminum fluoride stimulated phospholipase C, producing additional muscle activation.
Ratz
P H
PH
Department of Pharmacology, Eastern Virginia Medical School, Norfolk.
Blackmore
P F
PF
D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005263:Femoral Artery; D005459:Fluorides / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D012969:Sodium Fluoride / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D017607:Aluminum Compounds; D015220:Calcium Channels; D010656:Phenylephrine; D012969:Sodium Fluoride; D000535:Aluminum; D010738:Type C Phospholipases; D009543:Nifedipine; D005459:Fluorides; C032311:aluminum fluoride