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Role of cAMP and cGMP in arachidonic acid and PGE2 ‐induced cerebral vasodilation in newborn pigs
Author(s) -
Kanu Alie Joseph,
Leffler Charles W.
Publication year - 2010
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.24.1_supplement.979.5
Subject(s) - adenylyl cyclase , arachidonic acid , vasodilation , forskolin , phosphodiesterase 3 , soluble guanylyl cyclase , dilator , endocrinology , medicine , cyclooxygenase , nitric oxide , prostaglandin e , chemistry , phosphodiesterase , enzyme , biochemistry , stimulation , guanylate cyclase
Arachidonic acid (AA) metabolites of cyclooxygenase (COX) are important regulators of newborn cerebral circulation. PGE 2 stimulates cAMP in cultured vascular smooth muscle cells. PGE 2 increases cAMP and cGMP. Therefore, AA and PGE 2, generated in cerebral vessels may produce dilation by increasing cGMP and cAMP. In this study we address the hypothesis that cAMP and/or cGMP mediate dilation produced by AA and PGE 2 . Experiments used anesthetized newborn pigs with closed cranial windows. In piglets with PGE 2 , indomethacin (5mg/k g iv) was administered to inhibit COX. Pial arteriolar responses to AA (10 −7 M, 10 −5 M), PGE 2 (10 −7 M, 10 −5 M) or vehicle with guanylyl cyclase inhibitor ODQ (2.5 x10 −5 M) or adenylyl cyclase inhibitor SQ22536 (10 −6 M), or their vehicles were determined. ODQ (2.5 x10 −5 M) blocked AA‐ and PGE 2 ‐induced increases in cerebral vasodilation in newborn pigs. SQ 22536 blocked dilation produced by the adenylyl cyclase activator forskolin (10 −7 M) and also inhibited AA‐ and PGE 2 ‐induced cerebral vasodilation. Both cGMP and cAMP appear to contribute to the dilator effect of AA and PGE 2 . Since both ODQ and SQ22536 blocked dilations to AA and PGE 2 , cAMP and cGMP may act in a sequential manner. Research supported by NIH/NHLBI.