AJP - Regulatory, Integrative and Comparative Physiology, Vol 255, Issue 6 929-R935, Copyright © 1988 by American Physiological Society
Renal dose response and pharmacokinetics of atrial natriuretic factor in dogs
P. Cernacek, E. Maher, J. C. Crawhall and M. Levy
Department of Physiology, McGill University, Montreal, Quebec, Canada.
The present studies investigated the dose-plasma level-response
relationships with the use of increasing doses of atrial natriuretic factor
[ANF-(99-126)] administered by constant infusion in conscious dogs. The
preinfusion plasma immunoreactive ANF increased 12, 19, 23, and 35 times
during 45-min consecutive infusions of 50, 75, 125, and 175 ng.kg-1.min-1,
respectively. Over this pharmacological range, natriuresis increased
linearly with the infused dose (r = 0.99, n = 5) to a maximum response of
+1,550%, despite the significant gradual fall of blood pressure, which
attained a minimum of 83 mmHg (-26%) at 125 ng.kg-1.min-1. There was no
change of glomerular filtration rate (GFR) or renal plasma flow at any
dose. A very similar renal response was found in 13 other dogs infused with
the highest dose only in which the pharmacokinetic parameters of
ANF-(99-126) were estimated. Metabolic clearance rate during the infusion
was 1.09 +/- 0.19 l/min. The postinfusion decay curve of plasma
immunoreactive ANF was best described by a biexponential function. Plasma
disappearance half time was 1.44 min during the rapid phase and 10.3 min
during the slow phase of elimination. The results show that 1) natriuretic
response to ANF in the pharmacological range is dose dependent and occurs
despite a pronounced hypotension, 2) increase in GFR is not a prerequisite
of ANF-induced natriuresis, and 3) ANF is rapidly eliminated from the
circulation, suggesting an intensive uptake and/or degradation in the
target tissues.
