Modulation of exogenous and endogenous atrial natriuretic peptide by a receptor inhibitor

Tracy L. Stevens, Chi Ming Wei, Lawrence L. Aahrus, Denise M. Heublein, Masahiko Kinoshita, Yuzuru Matsuda, John C Jr. Burnett

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Atrial natriuretic peptide is an important peptide hormone of cardiac origin that functions to regulate cardiac preload via the regulation of sodium excretion. This natriuretic action occurs through activation of the particulate guanylyl cyclase-linked natriuretic peptide-A receptor. HS-142-1 is a newly discovered antagonist of the natriuretic peptide-A receptor that permits insight into the functional role of atrial natriuretic peptide in cardiorenal homeostasis. The first objective of this study was to define for the first time the intrarenal action of HS-142-1 on exogenous atrial natriuretic peptide-mediated natriuresis in anesthetized normal dogs. In group 1 (n=6), which received intravenous atrial natriuretic peptide at 100 ng/kg per minute, intrarenal HS-142-1 (0.5 mg/kg bolus) attenuated atrial natriuretic peptide-induced increases in glomerular filtration rate, urine flow, sodium excretion, and renal cyclic GMP generation and decreases in distal tubular sodium reabsorption. The second objective was to determine whether endogenous atrial natriuretic peptide participates in the regulation of basal sodium excretion. In group 2 (n=6), intrarenal HS-142-1 alone decreased both absolute and fractional sodium excretion and renal cyclic GMP generation and increased distal tubular sodium reabsorption. These studies demonstrate that HS-142-1 markedly attenuates exogenous atrial natriuretic peptide-mediated natriuresis via enhancement of distal tubular reabsorption and blunting of increases in glomerular filtration rate. Second, the current studies support a functional role for endogenous atrial natriuretic peptide in the regulation of basal sodium excretion.

Original languageEnglish (US)
Pages (from-to)613-618
Number of pages6
JournalHypertension
Volume23
Issue number5
StatePublished - May 1994

Fingerprint

Atrial Natriuretic Factor Receptors
Atrial Natriuretic Factor
Sodium
Natriuretic Peptides
Natriuresis
Peptide Receptors
Cyclic GMP
Glomerular Filtration Rate
Peptide Hormones
Guanylate Cyclase
Homeostasis
HS 142-1
Urine
Dogs

Keywords

  • antagonist
  • atrial natriuretic peptide
  • guanosine cyclic monophosphate
  • receptor, atrial natriuretic peptide
  • sodium

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Stevens, T. L., Wei, C. M., Aahrus, L. L., Heublein, D. M., Kinoshita, M., Matsuda, Y., & Burnett, J. C. J. (1994). Modulation of exogenous and endogenous atrial natriuretic peptide by a receptor inhibitor. Hypertension, 23(5), 613-618.

Modulation of exogenous and endogenous atrial natriuretic peptide by a receptor inhibitor. / Stevens, Tracy L.; Wei, Chi Ming; Aahrus, Lawrence L.; Heublein, Denise M.; Kinoshita, Masahiko; Matsuda, Yuzuru; Burnett, John C Jr.

In: Hypertension, Vol. 23, No. 5, 05.1994, p. 613-618.

Research output: Contribution to journalArticle

Stevens, TL, Wei, CM, Aahrus, LL, Heublein, DM, Kinoshita, M, Matsuda, Y & Burnett, JCJ 1994, 'Modulation of exogenous and endogenous atrial natriuretic peptide by a receptor inhibitor', Hypertension, vol. 23, no. 5, pp. 613-618.
Stevens TL, Wei CM, Aahrus LL, Heublein DM, Kinoshita M, Matsuda Y et al. Modulation of exogenous and endogenous atrial natriuretic peptide by a receptor inhibitor. Hypertension. 1994 May;23(5):613-618.
Stevens, Tracy L. ; Wei, Chi Ming ; Aahrus, Lawrence L. ; Heublein, Denise M. ; Kinoshita, Masahiko ; Matsuda, Yuzuru ; Burnett, John C Jr. / Modulation of exogenous and endogenous atrial natriuretic peptide by a receptor inhibitor. In: Hypertension. 1994 ; Vol. 23, No. 5. pp. 613-618.
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