Although @entity2472 is dependent on @entity141 -induced @entity3999 phosphorylation, other mechanisms including @entity141 sensitization and time-dependent phenomena such as cytoskeletal and cellular reorganization may contribute to contractile events. We hypothesized that if arteriolar smooth muscle exhibits time-dependent behavior this may be manifested in differences in relaxation after short- and long-term exposure to contractile agonists. Studies were conducted in isolated arterioles pressurized to 70 mmHg. In initial experiments (n = 10), rate of relaxation was measured after acute (5 min) or prolonged (4 h) exposure to 5 microM @entity1063 (NE). Prolonged exposure to NE resulted in significantly (P < 0.05) increased time for relaxation in physiological salt solution. Rapid relaxation of vessels exposed to NE for 4 h was observed after superfusion with 0 mM @entity141 buffer, indicating that the alteration in relaxation was reversible and @entity141 dependent. A similarly impaired dilation was not observed with 4-h exposure to @entity4338 (75 mM). To determine mechanisms contributing to the effects of prolonged NE exposure, studies were performed in the presence of the microtubule depolymerizing agent @entity49030 (10 microM) or a series of @entity669 phosphorylation inhibitors. Although @entity49030 caused significant vasoconstriction (P < 0.05) and potentiated NE vasoconstriction, it did not prevent the effect of long-term NE exposure on relaxation. @entity670 , although having no effect on acute NE-induced contraction, concentration-dependently inhibited prolonged NE constriction. Similarly, @entity7242 ( @entity13977 ) and p42/44 MAP kinase ( @entity4286 ) inhibitors prevented maintenance of long-term NE contraction. The data indicate that prolonged exposure to NE induces biochemical alterations that impair relaxation after removal of the agonist. The contractile effects are @entity141 dependent and involve @entity669 phosphorylation but do not appear to involve the polymerization state of the microtubule network.

Delayed arteriolar relaxation after prolonged agonist exposure: functional remodeling involving XXXX phosphorylation.

@entity49030 :: ('MESH:D003703', 'Chemical') :: ['demecolcine'] @entity7242 :: ('6714', 'Gene') :: ['Src'] @entity670 :: ('MESH:D019833', 'Chemical') :: ['Genistein'] @entity4286 :: ('MESH:C093973', 'Chemical') :: ['PD-98059'] @entity13977 :: ('5464', 'Gene') :: ['PP1'] @entity3999 :: ('79784', 'Gene') :: ['myosin'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['norepinephrine'] @entity4338 :: ('CHEBI:32588', 'Chemical') :: ['KCl'] @entity2472 :: ('MESH:C536214', 'Disease') :: ['arteriolar contraction']
@entity669 :: (CHEBI:18186,Chemical) :: ['tyrosine']
