Urinary excretion of renin and its biochemical properties in dogs.

Abstract

TOKIHITO YUKIMURA, KATSUYUKI MIURA, YOHKAZU MATSUSHIMA, FUMIHIKO IKEMOTO, AND KENJIRO YAMAMOTO SUMMARY The amount and biochemical properties of renin excreted by anesthetized dogs were investigated to elucidate the significance of urinary excretion in the metabolism of renin. Mean arterial blood pressure was 127 ± 4 mm Hg, renal blood flow was 170 ± 8 ml/min, glomerular filtration rate, 38.6 ± 2.3 ml/min, and urine flow rate, 0.37 ± 0.09 ml/min (n = 11). Urinary renin concentration (URC) was 9.2 ± 2.1 ng angiotensin I (ANG I)/ml-hr (n = 11), as determined by radioimmunoassay for ANG I generated by incubation with semipurified homologous renin substrate. The ANG I-producing activity was inhibited by more than 90% by a specific antibody to dog kidney renin. The renin secretion rate from the left kidney into the renal vein was 76.4 ± 13.3 ng ANG 1/ ml-hr per min (n = 11), and the simultaneous urinary excretion rate of renin was 2.3 ± 0.4 ng ANG 1/ ml-hr per min(n = 11). Molecular weight of the urinary renin was 40,000 daltons. The pH dependent curves of the angiotensin-forming capacity of renin showed an optimum between pH 5.5 to 6.0, and the estimated Michaelis constant was 0.42 /J,M. These biochemical parameters were similar to the findings in the case of renin in the plasma and the kidney. Moreover, neither acid nor trypsin treatment altered the renin activity in the urine. Thus, the active form of renin with a molecular weight 40,000 was excreted into the urine in dogs. Urinary excretion of renin was a small percentage of the renin secretion rate, thereby indicating the minor role of urinary excretion in the metabolism of renin. (Hypertension 6: 837-842, 1984) KEY WORDS • antirenin antibody • renin secretion rate high performance liquid chromatography

Fate of recombinant human renin administered exogenously to anesthetized monkeys.

“…Cumulative excretion of 125 I-rh-renin into the urine up to 120 minutes was less than 2% of the injected dose (n = 3), thereby indicating the negligible urinary excretion of renin, a finding consistent with the data in the dog 24 and rat. 6 HPLC profiles of liver and kidney extracts at 30 and 120 minutes showed two major peaks, including immunoreactive l23 I-rh-renin and the degradation products with a low molecular weight (Figure 6).…”

Physiology of the (pro)renin receptor: Wnt of change?

“…Given that the antibody they used targets the C terminus of the (P)RR/ ATP6ap2, it is not clear whether the main form at the membrane is the full protein or the furin-cleaved M8-9 fragment initially described by Ludwig et al 8 Moreover, (P)RR/ATP6ap2 is located on the luminal membrane of the intercalated cells and, thus, can only interact with (pro)renin in the urine. Indeed, prorenin and renin have been found in the urine of animals and humans, 105,106 but it is not clear whether under physiological conditions the urinary concentrations reach sufficient levels to initiate (P)RR/ATP6ap2 signaling. (Pro)renin is, however, also produced in neighboring principal cells and may induce a paracrine interaction.…”

Ser84 of Human Renin Contributes to the Biphasic pH Dependence of the Renin-Angiotensinogen Reaction

“…3) On the other hand, renin ordinarily has a neutral optimum pH (pH 6.0-8.0), and does not show a typical bell shape in pH dependence against homologous and heterologous angiotensinogens. [4][5][6][7][8][9] The reason for this unique pH dependence has not been elucidated, although Tyr83, 10) Ser84, 11) and Ala317 12) of human renin and His9 11) of a synthetic substrate have been reported to contribute to the pH dependence of the renin-angiotensinogen reaction. The catalytic mechanism of renin is generally thought to be analogous to that of a typical aspartic proteinase, but this cannot explain the neutral optimum pH and the unique pH profile of the renin reaction.…”