Effects of small C-ANF receptor ligands on plasma levels of atrial natriuretic factor, blood pressure, and renal function in the rat.
In this article, after a very brief review on ANF receptors, we report our study on the effects of small C-ANF receptor ligands in the rat. Two small ligands were synthesized: 2-naphthoxyacetyl-isonipecotyl-rANF11-15-NH2 (5 aa), containing 5 amino acids; and Ala7-rANF8-17-NH2 (10 aa), containing 10 amino acids from the ring structure of ANF1-28. After control periods, 5 aa or 10 aa were infused i.v. at a dose of 10 micrograms.min-1.kg-1 body weight for 70 min in anesthetized rats, followed by a 60-min recovery period. The 5 aa and 10 aa peptides significantly and reversibly increased plasma levels of endogenous immunoreactive ANF by 106 +/- 29 and 52 +/- 24 pg/mL, respectively. Infusion of the 5 aa peptide significantly decreased mean arterial blood pressure from 113 +/- 1 to 100 +/- 3 mmHg (1 mmHg = 133.32 Pa) and increased glomerular filtration rate from 1.6 +/- 0.2 to 2.3 +/- 0.2 mL/min, sodium excretion from 0.6 +/- 0.3 to 3.4 +/- 0.4 mumol/min, and potassium excretion from 0.5 +/- 0.2 to 1.2 +/- 0.2 mumol/min. Similar results were obtained with the 10 aa peptide. The effects of both peptides on blood pressure and sodium excretion persisted throughout the recovery period. The results confirm and extend previous observations showing that C-ANF receptors mediate the removal of ANF from the circulation. The shortening of the minimal peptide length necessary to bind to C-ANF receptors markedly enhances the possibility of developing orally active C-ANF receptor ligands for the treatment of cardiovascular and renal diseases.
Okolicany
J
J
Department of Physiology, Cornell University Medical College, New York, NY 10021.
McEnroe
G A
GA
Gregory
L C
LC
Lewicki
J A
JA
Maack
T
T
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D005919:Glomerular Filtration Rate; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008024:Ligands; D008297:Male; D008969:Molecular Sequence Data; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects
D007457:Iodine Radioisotopes; D008024:Ligands; D011956:Receptors, Cell Surface; C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor; D012964:Sodium; D017461:Receptors, Atrial Natriuretic Factor; D011188:Potassium