title: Effect of a ring-deleted atrial natriuretic factor analogue on ovine fetal renal and cardiovascular function.
abstract: The proposed actions of atrial natriuretic factor (ANF) are mediated through specific plasma membrane (R1) receptors coupled to guanylate cyclase. A second receptor, R2, has been characterized by its ability to bind to an acyclic, truncated ANF analog (C-ANF4-23). The ANF-R2 receptor has not been identified in the fetus. Our study was conducted to determine the effects of C-ANF on fetal renal and cardiovascular function and plasma ANF clearance rates. Chronically catheterized ovine fetuses (n = 6) at 111 to 117 d gestation (term 145 d) received a C-ANF infusion (1 microgram/min/kg) for 30 min followed by a combined infusion of C-ANF and ANF (C-ANF, 1 microgram/min/kg; ANF, 100 ng/min/kg) for an additional 30 min. C-ANF infusion significantly increased (mean +/- SEM) plasma ANF concentration (437 +/- 45 to 1067 +/- 297 pg/mL), urinary flow rate (0.26 +/- 0.04 to 0.38 +/- 0.07 mL/min/kg), sodium excretion (12.9 +/- 3.5 to 21.7 +/- 6.1 mumol/min/kg), and osmolar clearance (0.14 +/- 0.02 to 0.21 +/- 0.04 mL/min/kg) (p less than 0.05). The combined C-ANF/ANF infusion further increased plasma ANF concentration to 2394 +/- 532 pg/mL and resulted in significant increases in urinary flow rate, sodium excretion, osmolar clearance, GFR, and free water clearance compared with C-ANF infusion alone (p less than 0.05). These renal responses, however, were not significantly different from the responses to ANF infusion alone (100 ng/min/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, UCLA School of Medicine, Torrance.
authors.forename: R
authors.initials: R
authors.lastname: Castro
authors.forename: M G
authors.initials: MG
authors.lastname: Ervin
authors.forename: R D
authors.initials: RD
authors.lastname: Leake
authors.forename: M G
authors.initials: MG
authors.lastname: Ross
authors.forename: D A
authors.initials: DA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D011247:Pregnancy; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D012756:Sheep
chemical_list: D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C065367:atrial natriuretic factor (4-23)NH2, de-Gln(18)-de-Ser(19)-de-Gly(20,22)-de-Leu(21)-; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor