Elevated glucose concentration and natriuretic peptides receptor response on vascular smooth muscle of spontaneously hypertensive rats.
1. Hyperglycaemia is believed to be a major cause of diabetic vascular complications such as accelerated atherosclerosis. In order to elucidate the effect of hyperglycaemia on vascular response in spontaneously hypertensive rats (SHR), the natriuretic peptides receptor responses to vascular smooth muscle cells (VSMC) which are thought to suppress atherosclerosis were studied under high glucose (HG:22.2 mmol/L) conditions. 2. The total number of cells in SHR is higher and natriuretic peptides receptor response is smaller than that of cells in the Wistar-Kyoto (WKY) rat. Membrane bound protein kinase C (PKC) activity in HG or SHR is higher compared to that of cells in normal glucose (NG:5.6 mmol/L) or WKY. Cells cultured in HG for at least 2 passages had higher total cell number and receptor mediated cGMP formation were suppressed compared to cells cultured in NG both in SHR and WKY. Specific PKC inhibitor PKC (19-36) 1 mu mol/L prevented HG induced suppression of natriuretic peptides response. 3. These results show that hyperglycaemia may be linked to suppressed natriuretic peptides receptor response which is caused by increased PKC activity both in WKY and SHR. This suppressed response may cause the accelerated atherosclerosis by hyperglycaemia.
Yasunari
K
K
First Department of Internal Medicine, Osaka City University Medical School, Abeno-ku, Japan.
Kohno
M
M
Kano
H
H
Hanehira
T
T
Minami
M
M
Ikeda
M
M
Horio
T
T
Yokokawa
K
K
Takeda
T
T
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis*; D018000:Receptors, Peptide / Q000096:biosynthesis*
D009419:Nerve Tissue Proteins; D011506:Proteins; D018000:Receptors, Peptide; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D011493:Protein Kinase C; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D005947:Glucose