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Protein Kinase G attenuates myofilament Ca++ sensitivity in ovine adult but not fetal cerebral arteries via mechanisms ablated by chronic hypoxia
Author(s) -
Williams James Michael,
Pearce William Julian
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.627.5
Subject(s) - medicine , endocrinology , contractility , hypoxia (environmental) , cerebral arteries , myofilament , fetus , rho associated protein kinase , chemistry , biology , phosphorylation , myocyte , pregnancy , biochemistry , oxygen , genetics , organic chemistry
Chronic hypoxia modulates contractility and Protein Kinase G (PKG) activity differentially in fetal and adult ovine cerebral arteries. Because PKG can modulate contractility via inhibition of myofilament Ca++ sensitivity, the present study explores the hypothesis that chronic hypoxia induces changes in PKG activity that yield age‐dependent changes in myofilament Ca++ sensitivity. Middle cerebral arteries from non‐pregnant adults and term fetal sheep were prepared for measurements of contractile force and cytosolic Ca++ (Fura‐2) during responses to graded concentrations of 5HT in the presence and absence of 10 µM 8‐pCPT‐cGMP (a PKG activator). In normoxic adult arteries: 1) 8‐pCPT‐cGMP depressed 5HT‐induced increases in both [Ca++] and Ca++ sensitivity; 2) chronic hypoxia depressed Ca++ sensitivity but increased 5HT‐induced increases in [Ca++]; and 3) hypoxia ablated inhibition of Ca++ sensitivity by 8‐pCPT‐cGMP. In normoxic fetal arteries: 1) 8‐pCPT‐cGMP depressed 5HT‐induced increases in [Ca++] without effect on Ca++ sensitivity; 2) chronic hypoxia depressed Ca++ sensitivity but increased 5HT‐induced increases in [Ca++]; and 3) 8‐pCPT‐cGMP was without effect in hypoxic arteries. These results suggest that chronic hypoxia and PKG attenuate myofilament Ca++ sensitivity via a common mechanism that is absent in fetal cerebral arteries. Supported by USPHS Grants HL54120, HD31266, & HL64867.