The cellular mechanisms underlying smooth muscle hypoxic relaxation were examined in experiments on isolated chemically skinned muscle strips of rat portal vein. Low PO2 (3.9 kPa) shifted the pCa-tension relation to the right by 0.29 +/- 0.01 pCa units as compared to control curves (PO2, 18.8 kPa). Thus the Ca2+ sensitivity of the filaments had decreased. Addition of cyclic AMP (30 mumol l-1) with theophylline (5 mmol l-1) to the buffer solution produced a similar shift to low PO2. Low PO2 also decreased the maximal force to 40-50% of control. Inclusion of sodium fluoride (10 mmol l-1) and aluminium chloride (10 mumol l-1) in a bath solution caused partial (25-30%) relaxation of skinned smooth muscle preconstricted with 10 mumol l-1 Ca2+. The rate and amplitude of smooth muscle relaxation at low PO2 were significantly decreased by tolbutamide (5 mmol l-1), which is known to inhibit cyclic AMP-dependent protein kinases. We suggest that PO2 changes can alter myofilament responsiveness to Ca2+ and this effect may be related to cyclic AMP-dependent phosphorylation of myosin light chain kinase, its inactivation and subsequent uncoupling between Ca2+ and contractile machinery in smooth muscle.

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