title: Mechanisms underlying pervanadate-induced contraction of rat cremaster muscle arterioles.
abstract: The current study examined the role of extracellular Ca2+, calmodulin and myosin light-chain kinase (MLCK) in pervanadate-induced constriction of cannulated, pressurized rat cremaster arterioles. Pervanadate (0.03-100 microM) induced a concentration-dependent constriction of arterioles that was significantly attenuated (P<0.05) by the tyrosine kinase inhibitor tyrphostin 47 (30 microM). The L-type voltage-sensitive Ca2+ channel antagonists verapamil (10 microM) and nifedipine (1 microM) dilated vessels possessing myogenic tone but had no demonstrable effect on pervanadate constriction, while a higher concentration of nifedipine (10 microM) reduced constriction by approximately 50%. Pervanadate-induced contractions were reduced by the calmodulin inhibitor W-7 (N-(6-aminohexyl)-chloro-1-naphtalene sulphonamide, 50 microM) and the MLCK inhibitor ML-7 (1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine, 10 or 30 microM). Removal of extracellular Ca2+ abolished the contractile effect of pervanadate. Measurement of changes in arteriolar wall [Ca2+] using the Ca2+ sensitive dye Fura-2 showed that pervanadate did not increase [Ca2+] during arteriolar constriction. These observations suggest that pervanadate-induced contraction of smooth muscle in the cremaster arteriole involves Ca2+/calmodulin-dependent myosin phosphorylation and possibly sensitization of the contractile apparatus to Ca2+.
authors.affiliation: Microvascular Biology Group, School of Medical Sciences, RMIT University, PO Box 71, 3083 Bundoora, Victoria, Australia. t.murphy@rmit.edu.au
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Murphy
authors.forename: Brian E
authors.initials: BE
authors.lastname: Spurrell
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hill
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D020032:Tyrphostins / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001381:Azepines; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D013449:Sulfonamides; D020032:Tyrphostins; C076715:pervanadate; C070571:ML 7; C060152:tyrphostin 47; D005576:Colforsin; D014638:Vanadates; C017967:W 7; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009219:Myosin-Light-Chain Kinase; D017027:Protein Tyrosine Phosphatases; D009543:Nifedipine; D002118:Calcium