Cellular stress inhibits vascular smooth muscle relaxation.
OBJECTIVE
Cellular stress has been shown to induce a group of proteins called heat shock proteins (HSPs). Recent evidence suggests that a group of small HSPs may modulate vascular smooth muscle contraction (HSP27) and/or relaxation (HSP20). In this investigation, we hypothesized that cellular stress would alter contraction and/or relaxation of intact vascular smooth muscles and would lead to changes in the induction and/or phosphorylation of the small HSPs.


METHODS
Bovine carotid arteries were obtained from an abattoir, and physiologic contractile responses were determined in a muscle bath. Phosphorylation state-specific antibodies were produced and characterized against HSP27. Phosphorylation events were determined with phosphorylation state-specific antibodies or whole-cell phosphorylation and two-dimensional gel electrophoresis.


RESULTS
Cellular stress induced by arsenite or heat shock did not alter basal tone or the magnitude of contractions induced by serotonin or high extracellular potassium chloride. However, cellular stress led to inhibition of forskolin and sodium nitroprusside-induced vasorelaxation. This impaired vasorelaxation was associated with increases in the phosphorylation of HSP27 and decreases in forskolin-induced phosphorylation of HSP20.


CONCLUSIONS
Cellular stress, which leads to increases in the phosphorylation of HSP27, inhibits cyclic nucleotide-dependent vascular relaxation and cyclic nucleotide-dependent increases in the phosphorylation of HSP20.
Knoepp
L
L
Department of Surgery, Medical College of Georgia, Augusta, GA 30912, USA.
Beall
A
A
Woodrum
D
D
Mondy
J S
JS
Shaver
E
E
Dickinson
M
M
Brophy
C M
CM
D000818:Animals; D000918:Antibody Specificity; D018053:Arsenites / Q000494:pharmacology; D002339:Carotid Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D010452:Peptide Biosynthesis / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D017670:Sodium Compounds / Q000494:pharmacology
D018053:Arsenites; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D017670:Sodium Compounds; C017947:sodium arsenite