Atrial natriuretic factor influences in vivo plasma, lung and aortic wall cGMP concentrations differently.
Atrial natriuretic factor (ANF) promotes natriuresis and diuresis, increases vascular permeability and may induce peripheral vasodilatation. Endothelium-derived relaxing factor (EDRF), which is nitric oxide (NO), promotes local vasodilatation. ANF and EDRF-NO both cause vascular relaxation by generating cGMP via the activation of the particulate and soluble guanylate cyclases, respectively. This study examines the in vivo effect of exogenous ANF administration in normal Wistar rats, and of increased endogenous ANF in an experimental model of heart failure, on plasma and tissue cGMP concentrations. Low-dose ANF increased plasma and pulmonary cGMP concentrations, whereas 10-fold higher doses were necessary to increase aorta cGMP concentrations. Rats with a myocardial infarction had increased plasma ANF and cGMP and pulmonary cGMP concentrations, but aorta cGMP concentration remained similar to that of sham-operated rats. NG nitro L-arginine methyl ester (L-NAME) was administered chronically to sham-operated and myocardial infarction rats to block NO-synthase: soluble guanylate cyclase activity. L-NAME did not lower the increase in plasma ANF concentration or in urinary, plasma or pulmonary cGMP concentration. In contrast, L-NAME reduced the aorta cGMP concentration 6-fold, despite an increased level of circulating ANF. In summary, the pathophysiological range of plasma ANF concentrations greatly increases plasma and pulmonary cGMP concentrations (by activating particulate guanylate cyclase), but has little influence on the aorta cGMP concentration (which remains mainly dependent on NO-synthase: soluble guanylate cyclase activity).
Unit 367 INSERM, Paris, France.
J F
JF
Arnal
A I
AI
el Amrani
J B
JB
Michel
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001012:Aorta, Abdominal; D001013:Aorta, Thoracic; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood
D009320:Atrial Natriuretic Factor; D001120:Arginine; D012083:Renin; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester