Infusion of recombinant human prorenin into rhesus monkeys. Effects on hemodynamics, renin-angiotensin-aldosterone axis and plasma testosterone.
Prorenin, the biosynthetic precursor of active renin, is present in high concentrations in the kidney and reproductive organs. We have proposed that prorenin may be the vehicle of local renin systems, separating the functions of circulating and tissue renin. In the present study, we investigated the effect of increasing plasma prorenin 3- to 4-fold by infusing recombinant prorenin, 400 ng/min for 40 min, into male rhesus monkeys. The prorenin was first warmed to 37 degrees C to reduce the endogenous renin activity to a minimum. The study included a 20 min baseline and a 40 min recovery period. Plasma prorenin increased from 72 +/- 14 ng/mL/h to a maximum of 246 +/- 18 ng/mL/h during the infusion (P less than .001) and fell to 169 +/- 23 ng/mL/h 40 min after the infusion was stopped. Active renin did not change significantly. Plasma aldosterone increased slightly during the prorenin infusion (by 13%) and returned to baseline during the recovery period (P less than .05 compared to the infusion period). Plasma testosterone fell significantly from 1.9 +/- 0.1 ng/mL to 1.6 +/- 0.1 ng/mL during the infusion and further to 1.4 +/- 0.1 ng/mL during the post-infusion period (P less than .05). Blood pressure fell slightly but not significantly. Heart rate, glomerular filtration rate and renal blood flow, as well as urine flow and urine sodium and potassium excretion showed no significant change. These results demonstrate that human recombinant prorenin is not converted to active renin in the circulation of rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)
Cornell University Medical College, New York City.
T
T
Lenz
J E
JE
Sealey
R W
RW
Lappe
C
C
Carilli
G T
GT
Oshiro
J D
JD
Baxter
J H
JH
Laragh
D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D004792:Enzyme Precursors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects; D008253:Macaca mulatta; D011994:Recombinant Proteins / Q000494:pharmacology; D012083:Renin / Q000097:blood / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013739:Testosterone / Q000097:blood*
D004792:Enzyme Precursors; D011994:Recombinant Proteins; D000808:Angiotensinogen; D013739:Testosterone; D012083:Renin