Atrial and brain natriuretic peptides inhibit the endothelin-1 secretory response to angiotensin II in porcine aorta.
We have recently shown that the porcine aorta releases immunoreactive endothelin-1 in a time-dependent way. Here, we examined the inhibition by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of endothelin-1 secretion after stimulation with angiotensin II (Ang II) by using porcine aorta. Ang II dose-dependently stimulated immunoreactive endothelin-1 secretion. Porcine ANP-(1-28) and porcine BNP-26 both inhibited such secretion in a dose-dependent way. The addition of a cyclic guanosine 5'-monophosphate (cGMP) analogue, 8-bromo-cGMP, reduced the immunoreactive endothelin-1 secretion after stimulation with Ang II. In cultured porcine endothelial cells the inhibition by porcine ANP-(1-28) and porcine BNP-26 of immunoreactive endothelin-1 secretion after stimulation with Ang II was paralleled by an increase in the cellular cGMP level. Rat ANP-(5-25) was weaker than porcine ANP-(1-28) in inhibiting immunoreactive endothelin-1 secretion and increasing cGMP in cultured cells. There was negative correlation between the percent decrease in immunoreactive endothelin-1 and the percent increase in cGMP. Neither porcine ANP-(1-28) nor BNP-26 affected the number or sensitivity of Ang II binding sites in cultured porcine endothelial cells. These results suggest that ANP and BNP inhibit endothelin-1 secretion after stimulation with Ang II, probably through a cGMP-dependent process.
Kohno
M
M
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Yokokawa
K
K
Horio
T
T
Yasunari
K
K
Murakawa
K
K
Takeda
T
T
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D011863:Radioimmunoassay; D013552:Swine
D016232:Endothelins; D009419:Nerve Tissue Proteins; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP