Angiotensin II stimulates endothelin-1 secretion in cultured rat mesangial cells.
The present study was designed to test two hypotheses: (1) that angiotensin II (Ang II) stimulates endothelin-1 secretion in cultured rat mesangial cells and (2) that atrial and brain natriuretic peptides (ANP and BNP) inhibit the above-mentioned secretion in these cells. Ang II stimulated immunoreactive (ir) endothelin-1 secretion in a concentration-dependent manner between 10(-8) M and 10(-7) M. The protein kinase C (PKC) inhibitors from two chemical classes, H7 and staurosporine, inhibited secretion following such stimulation. The stimulatory effect of Ang II was also abolished in the PKC-depleted cells. Rat ANP(1-28) and rat BNP-45, which are the respective major circulating forms of ANP and BNP in rats, potently inhibited Ang II-stimulated endothelin-1 secretion in a concentration-dependent manner. Inhibition by ANP and BNP of Ang II-stimulated endothelin-1 secretion was paralleled by an increase in the cellular level of cyclic guanosine 5'-monophosphate (GMP). The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, reduced the stimulated endothelin-1 secretion. Rat ANP(5-25) was less effective that rat ANP(1-28) with respect to inhibiting ir-endothelin-1 secretion and increasing cellular cyclic GMP. These findings indicate that Ang II stimulates endothelin-1 secretion in cultured rat mesangial cells by a mechanism probably involving activation of PKC, and that rat ANP and BNP inhibit this stimulated secretion through a cyclic GMP-dependent process.
Kohno
M
M
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Horio
T
T
Ikeda
M
M
Yokokawa
K
K
Fukui
T
T
Yasunari
K
K
Kurihara
N
N
Takeda
T
T
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000032:analysis; D016232:Endothelins / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D009419:Nerve Tissue Proteins; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009599:Nitroprusside; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D006152:Cyclic GMP