Heat-shock response is associated with enhanced contractility of vascular smooth muscle in isolated rat aorta.
Stress proteins have been implicated in pathological cardiovascular conditions. We hypothesized that a heat-shock response modulates contractility of vascular smooth muscles. Rat aortic ring preparations were mounted in organ baths, exposed to 42 degrees C for 45 min, and subjected to contractions. Expression of HSP70 and phosphorylation of myosin light chain were examined with immunoblots. Heat shock enhanced contractile response to KCl in parallel with HSP70 expression in rat aortic rings from 8 h but not 1 h after the end of heat shock. Heat shock also augmented vascular contractility to phenylephrine whether endothelium was intact or denuded. Treatment of heat shock-preconditioned aortic rings with Bay K8644, a calcium channel activator, but not treatment with phorbol dibutyrate (1 micromol/l), a protein kinase C activator, enhanced contractions of the rings as compared with those of the control. The levels of phosphorylation of myosin light chains after administration of phenylephrine in heat shock-preconditioned tissues were statistically significantly higher than those in control tissues. Pretreatment with wortmannin (300 nmol/l), an inhibitor of myosin light chain kinase, decreased both contractility and phosphorylation of myosin light chains in parallel. However, heat-shock response did not affect relaxation responses to either acetylcholine in endothelium-intact aortic rings or sodium nitroprusside in endothelium-denuded rings. These results suggest that the heat-shock response is associated with enhanced vascular smooth muscle contractility through a modulation of thick-filament regulation.
Kim
In Kyeom
IK
Department of Pharmacology, Kyungpook National University School of Medicine, 700-422, Daegu, Republic of Korea. inkim@knu.ac.kr
Park
Tae-Gyu
TG
Kim
Yeung Hyen
YH
Cho
Jun Woo
JW
Kang
Bong-Seok
BS
Kim
Choong-Young
CY
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018869:Heat-Shock Response / Q000187:drug effects / Q000502:physiology*; D015151:Immunoblotting; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D018994:Myosin Light Chains / Q000096:biosynthesis; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D002120:Calcium Channel Agonists; D018840:HSP70 Heat-Shock Proteins; D018994:Myosin Light Chains; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009219:Myosin-Light-Chain Kinase; D002118:Calcium; D000077191:Wortmannin