Nitric oxide regulates angiotensin II receptors in vascular smooth muscle cells.
The objective of this study was to determine whether an enhanced generation of nitric oxide (NO) causes regulation of angiotensin II receptors in vitro using rat vascular smooth muscle cells in culture. Chronic treatment of cells with a series of NO-generating drugs, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and isosorbide dinitrate for 18h dose and time-dependently decreased [125I]-angiotensin II binding to cells without any significant change in affinity. Induction of nitric oxide synthase following lipopolysaccharide (10 and 100 ng/ml) treatment of cells for 18 h increased basal nitric oxide synthase activity with a concomitant increase of nitrite and cyclic cGMP levels in the conditioned media. LPS treatment significantly (P < 0.05) decreased [125I]-angiotensin II binding to these cells, an effect that was significantly (P < 0.05) attenuated in the presence of NG-nitro-L-arginine methyl ester. In contrast, treatment of cells with atrial natriuretic factor, dibutyryl cGMP, 8-bromo-cGMP, NaNO2 or NaNO3 failed to significantly alter the affinity or number of [125I]-angiotensin II binding sites. These results suggest that NO regulates angiotensin II receptors in vitro through a cGMP-independent mechanism.
Cahill
P A
PA
Johns Hopkins Medical Institutions, Department of Surgery, Baltimore, MD 21287, USA.
Redmond
E M
EM
Foster
C
C
Sitzmann
J V
JV
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D008070:Lipopolysaccharides; D009573:Nitrites; D011945:Receptors, Angiotensin; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D003994:Bucladesine; D026423:S-Nitroso-N-Acetylpenicillamine; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010396:Penicillamine; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate