Pharmacokinetics and pharmacodynamics of atrial natriuretic peptide after bolus and infusion administration in the isolated perfused rat kidney.
We used the isolated perfused rat kidney to test the hypothesis that the renal pharmacokinetics and pharmacodynamics of atrial natriuretic peptide (ANP) are saturable and dependent on the method of administration. Wistar rat kidneys were perfused for 90 min after a bolus dose or continuous infusion of 45, 180, 450 ng of ANP. ANP clearance ranged from 3.27 to 2.28 ml/min after bolus administration. ANP clearance fell after infusion, resulting in a disproportionate increase in the ANP concentration with increasing infusion rate. The ANP half-life was unaffected by dose in the bolus group averaging 18 min. Increasing the ANP dose also increased the amount of Na excreted into the urine, but there were no differences between experimental groups. However, the area under the curve responsible for the natriuresis was 36 to 41% lower after infusion. Exogenous creatinine clearance, renal perfusion pressure and flow and renal vascular resistance were not affected. We conclude that the renal pharmacokinetics of ANP are saturable and are altered by the method of administration due to a down regulation of the ANP receptor. Furthermore, infusion of ANP should result in a greater net natriuresis due to resulting greater ANP concentrations at steady state and an apparent increased sensitivity of the kidney to ANP after infusion.
Brier
M E
ME
Department of Medicine, University of Louisville, Kentucky.
Harding
G B
GB
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000493:pharmacokinetics* / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D012964:Sodium; D017461:Receptors, Atrial Natriuretic Factor