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(Hypertension. 1996;28:159-168.)
© 1996 American Heart Association, Inc.

Articles

Possible Involvement of Phospholipase D and Protein Kinase C in Vascular Growth Induced by Elevated Glucose Concentration

Kenichi Yasunari; Masakazu Kohno; Hiroaki Kano; Koji Yokokawa; Takeshi Horio; Junichi Yoshikawa

the First Department of Internal Medicine, Osaka City (Japan) University Medical School.

Correspondence to Kenichi Yasunari, MD, Division of Hypertension and Atherosclerosis, First Department of Internal Medicine, Osaka City University Medical School, 1-5-7 Asahi-machi, Abeno-ku, Osaka 545, Japan.

Hyperglycemia is believed to be a major cause of diabetic vascular complications. To elucidate the effect of hyperglycemia on vascular response, we studied hyperproliferation, hypertrophy, and the natriuretic peptide response of vascular smooth muscle cells under high-glucose conditions. We observed that cells cultured in high glucose (22.2 mmol/L) showed hyperproliferation and hypertrophy and that natriuretic peptide receptor responses were suppressed compared with cells cultured in normal glucose (5.6 mmol/L). We also examined phospholipase D and protein kinase C activities and found that in high-glucose conditions such activities are higher than in cells cultured in normal glucose. The activation of phospholipase D was not prevented by coincubation with 1 µmol/L protein kinase C(19-36), a specific protein kinase C inhibitor, but the activation of protein kinase C was. Protein kinase C(19-36) also markedly attenuated vascular hyperproliferation and hypertrophy as well as glucose-induced suppression of natriuretic peptide receptor response. These results show that hyperglycemia may be linked to vascular hyperproliferation, hypertrophy, and a suppressed natriuretic peptide receptor response, which are caused by increased phospholipase D and protein kinase C activities.

Key Words: natriuretic peptides • glucose • muscle, vascular, smooth • protein kinases

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