Hirofumi Sokabe

Examination of angiotensin-like substances from renal and extrarenal sources in mammalian and nonmammalian species

Abstract We have examined angiotensin-like substances produced by incubating renal and extrarenal tissue extracts with homologous plasmas in representative species of vertebrate classes from teleosts to mammals. SE-Sephadex column chromatograms, ratios of oxytocic to pressor activity (O:P ratio), and susceptibilities to proteases were used as the criteria. Angiotensin-like substances from renal and extrarenal tissues in mammals did not differ from Asp 1 -Ile 5 -angiotensin I. The active substance derived with avian kidney showed a peak at the more acid site in the chromatogram, a low O:P ratio, and greater susceptibility to proteases. The substance from reptilian kidney was eluted at position similar to Asp 1 -Ile 5 -angiotensin I, but it had an increased O:P ratio. It was also more resistant to enzyme treatments. The substance from amphibian kidneys was also eluted at similar position, but minor activity appeared later. The main peak of the bullfrog material had lower oxytocic activity, and was more susceptible to proteases. Avian, reptilian, and amphibian angiotensin-like substances are probably different from the known angiotensins I or II. In the teleosts, two peaks were always seen in the chromatograms. A possibility that these two peaks were produced artificially has not yet been clarified. From each of the five different sources we obtained two peaks, which were distributed approximately at six different positions. They were more susceptible to proteases than known angiotensins I or II. Some peaks had increased oxytocic activity. The substances produced by the aglomerular kidney of Lophius litulon and by the corpuscles of Stannius of the carp had a common peak at an extremely basic site. Angiotensin-like substances of teleostean origin were also different from known angiotensins I or II.

Plasma renin activity in Japanese eels (Anguilla japonica) adapted to seawater or in dehydration

The hypothesis that the renin-angiotensin system regulates glomerular filtration rate (GFR) by constricting the efferent glomerular arterioles, was tested in the Japanese eels (Anguilla japonica) by determining the plasma renin activity (PRA). The fish was dehydrated by transfer to 100% and 50% sea water, or by removal from water. In all conditions, urine volume and GFR were decreased within 1 hr. In 100% sea water an initial increase in PRA for 0.5–8 hr was observed. On transfer to 50% sea water or exposure to air, PRA was unchanged or slightly increased for 2–24 hr. It is necessary to consider the possibility that angiotensin may act in this species on intrarenal and extrarenal sites other than the efferent arterioles.

Chemical structure and role of angiotensins in the vertebrates

Abstract We examined angiotensins, the active components of the renin-angiotensin system, from renal and extrarenal sources in various vertebrates. SE-Sephadex column chromatograms, ratios of oxytocic to pressor activity, and susceptibilities to proteases were used as criteria. Angiotensins from renal and extrarenal tissues in rats, rabbits, and mice did not differ from Asp 1 -Ile 5 -angiotensin I. The active substances derived from the renal tissue of birds, reptiles, amphibians and teleosts, and from the teleostean corpuscles of Stannius, were definitely different from the known angiotensin I or II, suggesting evolution of the active components in the renin-angiotensin system. The physiological role of the renin-angiotensin system is not yet known for either mammals or lower vertebrates. We have presented a hypothesis that the renin-angiotensin system regulates glomerular filtration rate (GFR) by constricting the efferent arterioles. Plasma renin activity (PRA) was determined in bull-frogs in the dehydrated or overhydrated states. PRA was also determined in Japanese eels, transferred from fresh water to 100 and 50% sea water, or removed from water. PRA was parallel with GFR in the bullfrogs of differently hydrated states, basically supportin the above hypothesis. The results in the eels were complex. On transfer to 50% sea water or exposure to air, PRA decreased more slowly than GFR. In 100% sea water, an initial increase in PRA for 1–4 hr was observed. Intrarenal and extrarenal sites of action of angiotensin in teleosts, other than the efferent arterioles, need to be considered. The results may suggest evolution of the sites of action in the renin-angiotensin system.

A case of Bartter's syndrome with abnormal renin response to salt load

A 12-year-old girl with hypokalemic alkalosis, hyperaldosteronism with normalblood pressure, hyperplasia of the juxtaglomerular apparatus, and dwarfism is reported. Impaired vascular response to angiotensin II as well as to norepinephrine was observed. Plasma renin activity was markedly elevated while the patient was on a normal diet, was increased further on a low sodium diet, but was not suppressed on a high sodium intake. The plasma angiotensinogen level was reduced.