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Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure.

Publication ,  Journal Article
Moe, GW; Canepa-Anson, R; Armstrong, PW
Published in: J Cardiovasc Pharmacol
May 1992

The pharmacokinetics of synthetic atrial natriuretic factor (ANF) and its effects on cyclic GMP, urinary sodium excretion, and hemodynamics were compared in 18 control subjects with normal hemodynamics and 12 patients with severe heart failure. Human 99-126 ANF was administered intravenously (0.2 micrograms/kg i.v. followed by 0.07 micrograms/kg/min for 30 min). As compared with controls, baseline plasma ANF concentration was higher in the heart failure group (329.2 +/- 166.1 vs. 33.6 +/- 17.3 pg/ml in controls, means +/- SD, p less than 0.01). Synthetic ANF increased plasma ANF concentration by similar amounts, but the elimination half-life (t 1/2) for synthetic ANF was longer in the heart failure group (6.5 +/- 2.6 vs. 3.8 +/- 0.8 min, p less than 0.05). Baseline plasma cyclic GMP concentration was higher in the heart failure group (13.8 +/- 6.8 vs. 4.2 +/- 2.2 pmol/ml, p less than 0.01) but ANF increased plasma cyclic GMP concentration to a lesser degree (14.4 +/- 7.6 pmol/ml, p less than 0.05 vs. 24.9 +/- 10.1 pmol/ml, p less than 0.001). Baseline urinary sodium excretion was less in the heart failure group (13.3 +/- 14.0 vs. 53.7 +/- 37.3 mumol/min, p less than 0.01) and ANF induced a smaller increase in urinary sodium excretion (22.1 +/- 32.3 mumol/min, p less than 0.05 vs. 305.7 +/- 242.9 mumol/min, p less than 0.001). Baseline plasma norepinephrine (NE), renin, and aldosterone were higher in the heart failure group. Synthetic ANF increased plasma NE only in the control group, had no effect on renin, and decreased aldosterone in both groups. Hemodynamic responses were similar in both groups except the decreased arterial blood pressure (BP) was accompanied by increased heart rate (HR) only in the controls. Therefore, in heart failure, the t 1/2 of ANF is prolonged and there appears to be a limit for further increase in cyclic GMP. These changes may explain in part the blunted renal response to ANF.

Duke Scholars

Published In

J Cardiovasc Pharmacol

ISSN

0160-2446

Publication Date

May 1992

Volume

19

Issue

5

Start / End Page

691 / 700

Location

United States

Related Subject Headings

  • Sodium
  • Renin
  • Norepinephrine
  • Middle Aged
  • Male
  • Injections, Intravenous
  • Humans
  • Hemodynamics
  • Heart Rate
  • Heart Failure
 

Citation

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Moe, G. W., Canepa-Anson, R., & Armstrong, P. W. (1992). Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure. J Cardiovasc Pharmacol, 19(5), 691–700.
Moe, G. W., R. Canepa-Anson, and P. W. Armstrong. “Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure.J Cardiovasc Pharmacol 19, no. 5 (May 1992): 691–700.
Moe GW, Canepa-Anson R, Armstrong PW. Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure. J Cardiovasc Pharmacol. 1992 May;19(5):691–700.
Moe, G. W., et al. “Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure.J Cardiovasc Pharmacol, vol. 19, no. 5, May 1992, pp. 691–700.
Moe GW, Canepa-Anson R, Armstrong PW. Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure. J Cardiovasc Pharmacol. 1992 May;19(5):691–700.

Published In

J Cardiovasc Pharmacol

ISSN

0160-2446

Publication Date

May 1992

Volume

19

Issue

5

Start / End Page

691 / 700

Location

United States

Related Subject Headings

  • Sodium
  • Renin
  • Norepinephrine
  • Middle Aged
  • Male
  • Injections, Intravenous
  • Humans
  • Hemodynamics
  • Heart Rate
  • Heart Failure