Natriuretic peptides inhibit mesangial cell production of endothelin induced by arginine vasopressin.
The present study examined the effects of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP, respectively) on endothelin-1 (ET-1) secretion after stimulation with arginine vasopressin (AVP), using cultured rat glomerular mesangial cells. AVP stimulated immunoreactive (ir) ET-1 secretion in a concentration-dependent manner via a receptor-mediated process. Rat ANP-(1-28) and rat BNP-45 potently inhibited this stimulated secretion in a concentration-dependent manner. Inhibition by ANP and BNP of AVP-stimulated ET-1 secretion was paralleled by an increase in the medium level of guanosine 3',5'-cyclic monophosphate (cGMP). The addition of a cGMP analogue, 8-bromo-cGMP, reduced the stimulated ET-1 secretion. CNP was much less effective than rat ANP-(1-28) or rat BNP-45 with respect to inhibiting irET-1 secretion and increasing cGMP levels. High-performance liquid chromatography indicated that the major component of irET-1 in the culture medium corresponds to ET-1-(1-21). These findings indicate that AVP stimulates ET-1 secretion in cultured rat mesangial cells and that rat ANP and BNP inhibit this stimulated secretion, probably through a cGMP-dependent process.
First Department of Internal Medicine, Osaka City University Medical School, Japan.
M
M
Kohno
T
T
Horio
M
M
Ikeda
K
K
Yokokawa
T
T
Fukui
K
K
Yasunari
K
K
Murakawa
N
N
Kurihara
T
T
Takeda
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D016232:Endothelins; D009419:Nerve Tissue Proteins; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP