Hemodynamic effects of atrial natriuretic factor clearance receptor occupancy in conscious sheep.
The present study examined the hemodynamic actions of a non-guanylate cyclase linked or "clearance" atrial natriuretic factor (ANF) receptor ligand--des[Gln116Ser117Gly118Leu119Gly120] ANF 102-121 (C-ANF 4-23)--in conscious sheep. The effect of this peptide on the duration and potency of the hypotensive action of ANF (99-126) was also studied. C-ANF (4-23), infused at 400 micrograms/h for 2 h, reduced blood pressure, cardiac output and stroke volume, and increased total peripheral resistance slightly. These changes were similar to those previously observed with infusion of 20 micrograms/h ANF (99-126) in sheep. Endogenous ANF concentration increased from 28 +/- 13 to 85 +/- 18 pg/mL after 80 min infusion of C-ANF (4-23). The duration of hypotensive action from injection of ANF (99-126) was increased almost two-fold during infusion of C-ANF (4-23), however the hypotensive potency of ANF (99-126) was similar both prior to and during infusion of C-ANF (4-23). These studies support the concept of the metabolism of ANF via clearance receptors, suggesting that long-term hemodynamic actions of endogenous ANF may be achieved via prolonged blockade of these clearance receptors.
Parkes
D G
DG
Howard Florey Institute of Experimental Physiology and Medicine, Parkville, Australia.
Coghlan
J P
JP
Lewicki
J A
JA
Scarborough
R M
RM
Scoggins
B A
BA
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D010446:Peptide Fragments / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000097:blood / Q000494:pharmacology*; D012756:Sheep; D013318:Stroke Volume / Q000187:drug effects
D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor