Effects of protein kinase C and NADPH oxidase on hypoxic vasoconstriction in lamprey dorsal aortas

Abstract

Hypoxic vasoconstriction (HV) in aortas from cyclostomes, the most primitive vertebrates, has been suggested as the antecedent to hypoxic pulmonary vasoconstriction, and HV has been demonstrated in aortic segments from every vertebrate class except Mammalia. A protein kinase C (PKC) dependent role for NADPH oxidase has been shown in hypoxic pulmonary vasoconstriction in mammals. In the present study we investigated the role of PKC and NADPH oxidase pathways on HV in isolated lamprey (petromyzon marinus) dorsal aortas (LDA) using standard myography. Treatment of LDA with bisindoylmaleimide (BIM), a PKC inhibitor, reduced HV, whereas the PKC activator farnesyl thiotriazole (FTT) augmented HV, but had no effect on an alpha‐adrenergic contraction. However, the PKC inhibitor H7, and the PKC activator phorbol myristic acid (PMA) had no apparent effect on HV in LDA. In addition, the NADPH oxidase inhibitor diphenyleneiodonium (DPI) did not affect the magnitude of HV, but significantly impaired relaxation upon return to normoxia. These findings suggest that PKC, but not NADPH oxidase, may be an important component of the phylogenetically ancient lamprey HV. Supported by a grant from the MedCen Foundation of the Medical Center of Central Georgia.