C-type natriuretic peptide in chronic renal failure and its action in humans.
We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and acts as an endothelium-derived relaxing peptide. To clarify the clinical significance of CNP in renal disorders, we examined the plasma level of CNP in patients with various cardiovascular diseases, including chronic renal failure (CRF) patients who were under hemodialysis therapy. We also investigated biological effects of intravenously-administered CNP (0.43 nmol/kg) by bolus injection from the peripheral vein in healthy volunteers and measured systemic hemodynamic variables, plasma levels of CNP, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, aldosterone and also urine volume, urinary excretions of sodium, potassium, chloride and cGMP. The plasma CNP levels in healthy humans (N = 13) was 1.4 +/- 0.6 fmol/ml. In CRF patients, the plasma CNP significantly increased up to 3.0 +/- 1.1 fmol/ml. The administration of CNP elicited significant increase of plasma cGMP level (from 4.77 +/- 1.25 to 8.33 +/- 1.59 pmol/ml 15 min after the administration) and of urinary cGMP excretion (from 30.7 +/- 4.3 to 74.9 +/- 13.4 nmol/30 min). Intravenously-administered CNP exerted significant diuretic (% increase: +117 +/- 85.0), natriuretic, kalliuretic and chloriuretic actions with the increase of endogenous creatinine clearance. CNP also elicited significant hypotensive actions (delta BPs/delta BPd: -4.3 +/- 1.3/-4.1 +/- 1.0 mm Hg) with the concomitant increase of heart rate (+7.6 +/- 2.6 bpm). Plasma aldosterone concentration significantly decreased from 45.4 +/- 2.3 to 35.4 +/- 4.9 pg/ml 30 minutes after the administration. Taken together, these results suggest a role for CNP in human renal function.
Igaki
T
T
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Itoh
H
H
Suga
S
S
Hama
N
N
Ogawa
Y
Y
Komatsu
Y
Y
Mukoyama
M
M
Sugawara
A
A
Yoshimasa
T
T
Tanaka
I
I
Nakao
K
K
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009419:Nerve Tissue Proteins / Q000097:blood; D011506:Proteins / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*
D009419:Nerve Tissue Proteins; D011506:Proteins; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D000450:Aldosterone; D009320:Atrial Natriuretic Factor