The aim of this study was to evaluate the protective or deleterious effects of endogenous nitric oxide (NO) on liver cells during hepatic ischemia-reperfusion (IR) in the rat.
A bstract. Monoclonal antibodies directed against human renin were obtained by the fusing of myeloma cells with spleen cells from Balb/c or highresponder Biozzi mice injected with pure tumoral or highly purified renal renin. These procedures resulted in the production of seven stable monoclonal antibodies to human renin. Antibodies in the hybridoma culture medium were screened by binding to pure iodinated renin or insolubilized renin in a solid phase assay. The concentration of purified antibodies that provided a 50% binding to iodinated renin varied from 1 X 10-10 to 1 X 10-7 M. Two monoclonal antibodies were found to be potent inhibitors of renin enzymatic activity in vitro, behaving as noncompetitive inhibitors (Ki, 1 to 4 X 10`s M). They were specific for primate renin. Three monoclonal antibodies provided suitable immunoadsorbants for renin purification. One of these immunoadsorbants was used for large-scale purification of the renal enzyme, resulting in an 825-fold renin enrichment in a single step. Two antibodies were able to distinguish between active and inactive renin and enabled concomitant separation and purification of the two enzyme forms in various biological fluids. Monoclonal antibodies also stained human and monkey renal renin when indirect immunofluorescence and peroxidase-antiperoxidase techniques were used. A highly sensitive radioimDr. Atlas is with the
Abstract. Renin biosynthesis was studied in a juxtaglomerular cell tumor. The tumoral tissue had a high renin content (180 Goldblatt Units/g of tissue), was heavily stained by immunofluorescence using human renin antiserum, and exhibited numerous characteristic secretory granules by electron microscopy. In one series of experiments, renin biosynthesis was studied in tissue slices, by following the incorporation of radiolabeled amino acids into specific immunoprecipitable renin. Time course studies showed that renin was first synthesized in a high molecular weight form, 55,000 mol wt, i.e., 10,000 mol wt higher than that of active renin, and was then converted into a 44,000-mol wt form. In a second series of experiments renin tumoral cells were cultured. Small, round, birefringent cells obtained after collagenase digestion produced renin in both primary culture and subculture media. After 5 d most of the renin found in the culture medium was inactive, but could be activated by trypsin treatment. The tumoral tissue exhibited a strong renin immunofluorescence and numerous secretory granules were observed by electron microscopy. In contrast, the renin-producing cells isolated from this tumor and grown in culture showed little renin immunofluorescence and no secretory granule could be observed. The renin-producing cells in primary culture and subculture
Antibodies were raised in rabbit against pure human renin. The antisera obtained are highly specific for human renin versus hog, dog and rat renin. They do not cross-react with acid proteases such as pepsin and human cathepsin D. A direct radioimunoassay is described for human renin in plasma and kidney extracts. 30 to 50 pg of enzyme (2.5 to 4 x 10(-5) Goldblatt units) are detected.
Spontaneously hypertensive Okamoto-strain rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were actively immunizedwith mouse renin to investigate the effect on blood pressure of blocking the renin-angiotensinogen reaction. Ten male SHR and 10 male WKY rats were immunizedwith purified mouse submandibular gland renin. Control rats were immunized with bovine serum albumin. Antirenin antibodies were produced by both SHR andWKY rats, but renin-immunized SHR had higher titers of circulating renin antibodies after three injections. The increase in renin antibody in renin-immunized SHR was associated with a significant drop in blood pressure (tail-cuff method) that became similar to that of theWKY control rats after four injections. The blockade by antirenin immunoglobulins of the renin-angiotensinogen reaction also decreased the blood pressure of normotensive rats. Perfusion of renin-immunized rats with mouse submandibular renin (10,g) in vivo caused no increase in blood pressure. Perfusion of renin-immunized, salt-depleted SHR with converting enzyme inhibitor caused no further decrease in blood pressure but significantly decreased blood pressure in salt-depleted control rats. The presence of circulating renin antibodies was associated with low plasma renin activity (0.31±0.23 ng angiotensin I [Ang I]/ml/hr). Plasma renin activity was unchanged in control animals (13.1±3.9 ng Ang ImlI/hr in control SHR, 13.9±3.2 ng Ang VImlIhr in control WKY rats). Renin antibody-rich serum produced a dose-dependent inhibition of rat renin enzymatic activity in vitro. The chronic blockade of the renin-angiotensinogen reaction in renin-immunized SHR produced an almostcomplete disappearance of Ang 11 (0.8±7fmol/ml; control SHR, 30.6±+15.7 fmol/ml) and a 50%o reduction in urinary aldosterone. Renin immunization was never associated with a detectable loss of sodium after either 10 or 24 weeks. The glomerular filtration rate was not decreased 10 weeks after renin immunization, whereas blood pressure was significantly decreased, plasma renin activity was blocked, and renal plasma flow was increased. The ratio of left ventricular weight to body weight after 24 weeks was significantly below control levels in renin-immunized WKY rats and SHR. Histological examination of the kidney of renin-immunized SHR showed a chronic autoimmune interstitial nephritis characterized by the presence of immunoglobulins, mononuclear cell infiltration, and fibrosis around the juxtaglomerular apparatus. These expenments demonstrate that chronic specific blockade of renin decreases blood pressure in a genetic model of hypertension in which the renin-angiotenisn system is not directly involved. It also offers a model for comparing chronic renin inhibition with other methods of blocking the renin-angiotensin system in the hypertensive rat. (Circulation 1990;81:1899-1910 T he most specific way to block the reninangiotensinogen. The renin-angiotensinogen reacangiotensin system is to inhibit its first and tion can be inhibited by passive administration of rate-limitin...
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