Chronic one-kidney hypertension in rabbits. II. Evidence for a new factor.

Skeggs, Leonard T.; Kahn, Joseph R.; Levine, Martin; Dorer, Frederic E.; Lentz, Kenneth E.

doi:10.1161/01.res.39.3.400

Cited by 7 publications

(2 citation statements)

References 28 publications

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“…spectroscopy (Haas et aL., 1953c). Since then heterogeneity ofrenin from a variety of species has been demonstrated by different methods (Morgan & Leon, 1963;Skeggs et al, 1967;Boyd, 1972;Skeggs et al, 1972; Rubin, 1972).…”

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confidence: 99%

A comparison of the properties of renin isolated from pig and rat kidney

Lauritzen¹,

Damsgaard²,

Rubin³

et al. 1976

Biochemical Journal

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1. On isoelectric focusing, renin from rat kidneys showed three activity peaks with pI values at pH 5.0, 5.2 and 5.4 after a purification procedure involving differential centrifugation, acidification, chromatography on Sephadex G-75 and dialysis. 2. The preparation (purified 140-fold) was compared with a crude kidney extract in the absence and presence of 3 M-urea by isoelectric focusing. The pattern of activity distribution was confirmed by these experiments and the content of isoenzymes in the three groups calculated. 3. Pig renin was prepared and compared with rat renin with regard to molecular weight, acid activation, behaviour on isoelectric focusing, immunogenicity and substrate affinity. 4. Extracts of rat kidney contained multiple forms of renin with mol.wt. between 39000and 42000, whereas active pig renin had an approximate mol.wt. of 40000. Acidification of rat renal extracts did not increase the activity of renin, indicating the absence of an inactive form of renin in rat kidneys, whereas pig renin was activated by this procedure. Pig renin has isoelectric points at pH 4.6, 4.8, 5.05 and 5.2, significantly lower than for rat renin. The isoenzymes from the two species had no antigenicity in common, as shown by crossed immunoelectrophoresis or rocket immunoelectrophoresis. 5. The Michaelis constants for pig and rat renin were in the same range, 1 X 10(-6) M, when rat renin substrate was used. The relative content of rat isoenzyme with pI in the pH ranges 4.9-5.1, 5.1-5.3 and 5.3-5.5 was approx. 20, 27 and 53% respectively. Purified pig renin prepared in two different ways had isoenzymes with pI in the pH regions 4.5-4.7, 4.7-4.9, 4.9-5.05 and 5.05-5.20 in the approximate proportions 14, 24, 28 and 29%.

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confidence: 99%

A comparison of the properties of renin isolated from pig and rat kidney

Lauritzen¹,

Damsgaard²,

Rubin³

et al. 1976

Biochemical Journal

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“…8) (6). Conversely, the absence or insufficiency of interspecies renin homology might explain the failure to obtain a blood pressure lowering or a short-lived hypotensive effect during active immunization (13)(14)(15)(16)(17)(18) when heterologous renin is used (13)(14)(15)(16)(17)(18). The choice of the normotensive marmoset has several other advantages: on a regular diet (i.e., rich in potassium and poor in sodium), the high plasma renin and aldosterone values indicate a chronic stimulation of the renin-angiotensin-aldosterone system.…”

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confidence: 99%

Active immunization against renin in normotensive marmoset.

Michel¹,

Guettier²,

Philippe³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Calfithrirjacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutaneous injections of 30 ,ug each, with complete and then incomplete Freund's adjuvant. Three The inhibition of the renin-angiotensin system at its first and rate-limiting step, the action of renin on angiotensinogen, can be achieved by the use of synthetic renin inhibitors (1) and by immunological tools. Indeed, the early studies on renin inhibition deal with passive or active immunization against renin (2-4). However, interpretation of such results is limited by the fact that renin was not completely purified. Thus, heterologous renin was used for immunization protocol, even though it is now known that renin has a very strong immunological specificity. Finally, only blood pressure was monitored in the earlier experiments, and no plasma renin activity or aldosterone assays were available. The renin antibody titer also could not be directly measured.The acute passive immunization of renovascular hypertensive dogs (5) and normotensive marmosets (6) with specific homologous renin antibodies clearly showed that the level of blood pressure depended on renin. From this latter study (6) it was concluded that renin regulated blood pressure in the normotensive marmoset ingesting its usual amount of sodium. The present study was designed to examine the effects of active immunization against renin in marmosets and to observe the effects of chronic blockade of the renin substrate reaction. (SBP) was also recorded once a week in unanesthetized animals by the tail-cuff method (BP recorder 8005, W+W Electronic, Appelex, Bagneux, France). The validation of the tail-cuff method for blood pressure measurement has been reported in normotensive (7) and hypertensive marmosets (8). Five marmosets were immunized by three repeated subcutaneous injections of 30 Ag of highly purified human renin (specific activity, 680 Goldblatt units per mg of protein). Purification was performed by immunoadsorption on a monoclonal antibody from ajuxtaglomerular cell tumor as described by Galen et al. (9). The first injections were performed in complete Freund's adjuvant (0.5 ml), the two others in incomplete Freund's adjuvant (0.5 ml). Three control animals received only the adjuvant. Injections were repeated at intervals of 3 weeks. MATERIALS AND METHODSIn Vitro Experiments. The presence of renin antibodies was determined by the ability of marmoset plasma to bind pure human iodinated renin. The titer was defined as the antiserum dilution able to bind 50% of the renin tracer. Plasma renin concentration was measured by radioimmunoassay (RIA) of angiotensin I generated by 1 hr of incubation of 1:50-diluted marmoset plasma in the presence of an excess (635 pmol/200 gl) of human angiotensinogen (6). When the...

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