In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 5 ( 1997-09-02), p. 1586-1592
Abstract:
Background NO is known to deactivate protein kinase C (PKC). Because we have reported that the activation of PKC activates ecto-5′-nucleotidase, we examined whether the inhibition of NO synthesis increases ecto-5′-nucleotidase activity through the activation of PKC. Methods and Results The left anterior descending coronary artery (LAD) was cannulated and perfused with blood through a bypass tube from the left carotid artery in 65 open-chest dogs. The intracoronary administration of N G -nitro- l -arginine methyl ester (L-NAME, 10 μg · kg −1 · min −1 ), an NO synthase inhibitor, for 30 minutes increased ( P 〈 .05) adenosine levels in coronary venous blood (123±10 versus 21±3 pmol/mL) and ecto-5′-nucleotidase activity (64±6 versus 41±4 nmol · mg −1 · min −1 ) in the LAD-perfused myocardium. The intracoronary administration of α,β-methyleneadenosine 5′-diphosphate, an inhibitor of ecto-5′-nucleotidase, or GF109203X or calphostin C, both of which are PKC inhibitors, attenuated the L-NAME–induced increases in adenosine levels and ecto-5′-nucleotidase activity. Treatment of cultured human coronary arterial endothelial cells (HCAECs) with L-NAME for 30 minutes increased ecto-5′-nucleotidase activity, which was inhibited by either GF109203X or calphostin C. NO releasers decreased both ecto-5′-nucleotidase and PKC activities in HCAECs. Treatment of HCAECs with zaprinast, a selective inhibitor of cGMP-specific phosphodiesterase, with or without atrial natriuretic peptide, increased intracellular cGMP concentrations but did not change ecto-5′-nucleotidase activity. Conclusions These results indicate that the inhibition of NO synthesis increases both adenosine production and ecto-5′-nucleotidase activity through the activation of PKC and that NO modulates ecto-5′-nucleotidase via cGMP-independent mechanisms.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.96.5.1586
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1997
detail.hit.zdb_id:
1466401-X
