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At least 19 recordsLinked to original sources

PubMed1977

Renin reactivity, renin activity and renin concentration in patients with normal and low renin essential hypertension.

Renin activity, concentration, substrate and reactivity were determined in normal subjects as well as in hypertensive subjects with suppressed and normal plasma renin activity. Renin substrate measurements were similar in all groups. Renin reactivity, a measure of circulating modifiers of the renin reaction, was significantly increased in both hypertensive groups. Reactivity was significantly greater in the normal renin hypertensive group than the low renin hypertensive group. Renin concentration was significantly suppressed in both hypertensive groups, but to a greater degree in the low renin hypertensives. These findings suggest that plasma renin concentration may be suppressed in most hypertensive subjects. Furthermore, plasma renin activity may be "normalized" in most hypertensive subjects by the effect of circulating modifiers of the renin reaction. While renin reactivity in the plasma of low-renin hypertensive subjects is accelerated to a lesser degree than that of the normal-renin hypertensives, this finding alone does not explain the low plasma renin activity.

Angiotensinogen↗

PubMed1983

Purification of high molecular weight (HMW) renin from porcine kidney and direct evidence that the HMW renin is a complex of renin with renin binding protein (RnBP).

The high molecular weight (HMW) renin was purified from porcine kidney by a procedure involving extraction with a buffer system containing protease inhibitors, ammonium sulfate fractionation, pepstatin-aminohexyl-Sepharose 4B column chromatography, gel filtration on Ultrogel AcA 44 and aminohexyl-Sepharose 4B column chromatography. The resulting preparation showed a single band on isoelectric focusing, exhibiting an isoelectric point at pH 5.25, and was stable on storage at -80 degrees C for 4 months. The specific activity was 3.97 mg of angiotensin I formed/mg of protein per h at 37 degrees C and at pH 6.5 with porcine angiotensinogen as the substrate. When the HMW renin was exposed to acid, renin activity increased by about 5-fold and the free form of fully active renin was recovered from the acidified HMW renin, leaving an insoluble aggregate of protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the HMW renin showed two protein bands, of which one was identified as renin from the electrophoretic mobility and the other was the protein, assigned as renin binding protein (RnBP), that was insolubilized by acidification. The purified HMW renin is a complex of renin with RnBP, and the molecular weights of RnBP and renin in the HMW renin were estimated to be 39,000 and 32,000, respectively, by gel permeation liquid chromatography in 6 M guanidine-HCl. A modified rapid method for purification of renin is also presented.

Animals↗

PubMed1981

In vitro determinants of plasma renin activity in serially-studied inbred dogs with neonatally induced coarctation hypertension: renin reactivity, renin substrate, and renin concentration.

Increased renin activity of plasma, suggesting an excess of circulating accelerators and/or deficit of inhibitors of the renin reaction, has been reported in a number of hypertensive states; however, its contribution to genesis and/or maintenance of hypertension is unknown. To longitudinally assess the evolution of plasma renin reactivity in relation to blood pressure in neonatally-induced coarctation hypertension, we have made serial observations in 6 coarcted dogs and in 7 littermate controls over 1-12 months post-aortic-banding during varied steady-state sodium intake. Measurements of renin activity (defined as the increment of angiotensin I-generation rate following addition of exogenous renin to plasma), renin substrate concentration (RS), and plasma renin activity (PRA), together with calculation of plasma renin concentration (PRC) (as PRC = PRA divided by renin reactivity) provided estimates of the three major determinants of PRA. RS values were adjusted for variability due to assay-control and to age via covariate analysis. Results indicate no difference in adjusted RS between coarcted and control dogs, thus obviating the influence of RS differences on renin reactivity results. Renin reactivity and PRC in coarcted dogs were also comparable to control values. Furthermore, responses of RS, renin reactivity and PRC to dietary sodium manipulation were similar in coarcted and control animals. We conclude that circulating modifiers of the renin reaction play no role in the genesis or in the first-year maintenance of neonatally-induced coarctation hypertension.

Animals↗

PubMed1984

Renin profiling to select antihypertensive baseline drugs. Renin inhibitors for high-renin and calcium entry blockers for low-renin patients.

Renin profiling stimulated research into the pathophysiology of essential hypertension and influenced the development of antihypertensive treatment strategies. Patients with a high renin value and usually younger age respond better to drugs that interfere with the renin-angiotensin system, that is, beta blockers or converting enzyme inhibitors. Patients with a low renin value and often older age respond better to calcium entry blockers or diuretics. Patients with normal renin levels exhibit mixed but, on average, equal responses to these types of drugs. A pathophysiology-oriented antihypertensive treatment strategy is proposed in which beta blockers or converting enzyme inhibitors are used as one and calcium entry blockers--in the place of diuretics when possible--as the other baseline drug, and this approach may provide a cardiac-protective effect.

Adrenergic beta-Antagonists↗

PubMed1984

Characterization of inactive renin ("prorenin") from renin-secreting tumors of nonrenal origin. Similarity to inactive renin from kidney and normal plasma.

Inactive renin comprises well over half the total renin in normal human plasma. There is a direct relationship between active and inactive renin levels in normal and hypertensive populations, but the proportion of inactive renin varies inversely with the active renin level; as much as 98% of plasma renin is inactive in patients with low renin, whereas the proportion is consistently lower (usually 20-60%) in high-renin states. Two hypertensive patients with proven renin-secreting carcinomas of non-renal origin (pancreas and ovary) had high plasma active renin (119 and 138 ng/h per ml) and the highest inactive renin levels we have ever observed (5,200 and 14,300 ng/h per ml; normal range 3-50). The proportion of inactive renin (98-99%) far exceeded that found in other patients with high active renin levels. A third hypertensive patient with a probable renin-secreting ovarian carcinoma exhibited a similar pattern. Inactive renins isolated from plasma and tumors of these patients were biochemically similar to semipurified inactive renins from normal plasma or cadaver kidney. All were bound by Cibacron Blue-agarose, were not retained by pepstatin-Sepharose, and had greater apparent molecular weights (Mr) than the corresponding active forms. Plasma and tumor inactive renins from the three patients were similar in size (Mr 52,000-54,000), whereas normal plasma inactive renin had a slightly larger Mr than that from kidney (56,000 vs. 50,000). Inactive renin from each source was activated irreversibly by trypsin and reversibly by dialysis to pH 3.3 at 4 degrees C; the reversal process followed the kinetics of a first-order reaction in each instance. The trypsin-activated inactive renins were all identical to semipurified active renal renin in terms of pH optimum (pH 5.5-6.0) and kinetics with homologous angiotensinogen (Michaelis constants, 0.8-1.3 microM) and inhibition by pepstatin or by serial dilutions of renin-specific antibody. These results indicate that a markedly elevated plasma inactive renin level distinguishes patients with ectopic renin production from other high-renin hypertensive states. The co-production of inactive and active renin by extrarenal neoplasms provides strong presumptive evidence that inactive renin is a biosynthetic precursor of active renin. The unusually high proportion of inactive renin in plasma and tumor extracts from such patients is consistent with ineffective precursor processing by neoplastic tissue, suggesting that if activation of "prorenin" is involved in the normal regulation of active renin levels it more likely occurs in the tissue of origin (e.g., kidney) than in the circulation.

Adult↗

PubMedDate not supplied

Nonproportional changes in plasma renin concentration, renal renin content, and rat renin messenger RNA.

The expression of the renin gene in rat kidneys was studied using mouse submaxillary gland renin complementary DNA. The length of rat renin messenger RNA (mRNA) was approximately 1600 nucleotides, similar to that of mouse submaxillary gland and kidney renin mRNA. Rat renin mRNA was quantified by a radiodensitometric complementary DNA hybridization assay. The effects of intense long-term stimulation and short-term inhibition of renin secretion on plasma renin concentration, renal renin concentration, and renin mRNA content were compared with those of controls. After 15 days of sodium depletion and captopril treatment, plasma renin concentration increased 46-fold, renal renin concentration only 1.5-fold, and renin mRNA content increased about threefold. Following a 1-hour infusion of angiotensin II in sodium-depleted and captopril-treated rats, plasma renin concentration decreased by 84% whereas no significant changes in either renal renin concentration or renin mRNA content were observed. These results show that sodium depletion and captopril treatment increase the level of renin gene transcription and renin biosynthesis. However, there are nonproportional changes in plasma renin levels, renal renin content, and its mRNA. These results suggest that newly synthesized renin is not stored in the kidney but is rapidly secreted into the blood. Short-term inhibition of plasma renin concentration by angiotensin II is most likely mediated by posttranslational mechanisms.

Angiotensin II↗

PubMed1986

Kinetic comparisons of amniotic fluid inactive renin and renal renin using synthetic and human renin substrates.

Inactive renin has been isolated from pooled amniotic fluid and purified approximately 642-fold. Prior to activation the isolates had approximately 4% of the activity found after activation. The observation is similar to that reported for inactive renin from chorionic cell culture and suggests a placental origin of amniotic fluid inactive renin. Using plasma from an estrogen-treated woman, renin substrate was recovered free of renin and inactive renin and a portion was separated into NMW and HMW components. The NMW form constituted approximately 93% and the HMW form approximately 7% of the renin substrate. Amniotic fluid inactive renin was used for determinations of enzyme-substrate kinetics with the pooled, NMW, and HMW plasma substrate and tetradecapeptide synthetic substrate, and the results were compared to similar determinations using standard renal renin. Using synthetic substrate, the kinetics of renal renin and amniotic fluid inactive renin before and after activation were similar. The kinetics of renal renin with pooled, NMW, and HMW plasma substrate were also similar. Amniotic fluid inactive renin had a lower Km with pooled than with NMW substrate, however, which resulted from a significantly smaller Km with HMW component. Although the affinity constants with pooled substrate were not different for renin and inactive renin, the Km of inactive renin was significantly less with the HMW component of plasma renin substrate. The observations are compatible with a role for placental inactive renin in normal pregnancy and suggest the possibility of a further role in hypertensive pregnancy.

Amniotic Fluid↗

PubMed1977

Renin reactivity in plasma of patients with normal renin and low renin essential hypertension.

Plasma renin reactivity (PRR) is the rate of angiotensin generation in vitro after addition of exogenous renin to plasma. To evaluate the hypothesis that suppressed plasma renin activity (PRA) in patients with low renin essential hypertension may be related to an alteration of the kinetics of the in vitro renin reaction, PRR was compared in plasma of patients with low renin and normal renin essential hypertension. Prostaglandin A (PGA) inhibits renin, and PGA was also measured to determine if suppressed PRA may be related to increased PGA. Low renin and normal renin hypertension were defined by comparing PRA responses of 30 hypertensive patients and 16 matched control subjects to upright posture and furosemide (80 mg p.o.). Nine of 30 patients had low PRA. Compared to that in plasma of patients with normal renin hypertension, PRR was suppressed (P less than 0.005) during 30, 60, and 180 min incubations in the low renin patients. Overall, in the hypertensive patients, there was a significant positive correlation (r= +0.58; P less than 0.01) between PRR and the PRA response to furosemide. PGA in patients with low renin hypertension (0.86 ng/ml+/-0.06 SE) was less (P less than 0.05) than that in patients with normal renin hypertension (1.10 ng/ml+/-0.07) SE) and control subjects (1.18 ng/ml+/-0.10 SE); PGA of normal renin patients and control subjects did not differ (P less than 0.1). These results suggest that an alteration of the kinetics of the renin reaction may contribute to the apparent renin suppression in patients with low renin hypertension. Hypertensive patients with suppressed PRA also have low PGA.

Carbon Dioxide↗

PubMed1994

Identification of vascular renin-binding proteins by chemical cross-linking: inhibition of binding of renin by renin inhibitors.

OBJECTIVE: To investigate the mechanism of tissue uptake of renin. DESIGN: Angiotensin peptide formation in tissues is dependent on kidney-derived renin, leading us to hypothesize that tissues possess a mechanism for uptake of renin from plasma. METHODS: The binding of [125I]-labelled renin to membranes prepared from various rat tissues was examined. [125I]-labelled renins were cross-linked to membranes with disuccinimidyl suberate and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by autoradiography. RESULTS: Mesenteric artery membranes bound both [125I]-labelled rat renin and [125I]-labelled mouse submandibular gland renin. Cross-linking experiments showed two bands, one of relative molecular mass approximately 105,000 and the other of approximately 75,000. After taking into account the molecular weight of renin, these bands represent renin-binding proteins of relative molecular mass approximately 70,000 and approximately 40,000, respectively. The highest level of these binding proteins was in the mesenteric artery; lower levels were found in the aorta, lung and renal medulla. Renin-binding proteins were also identified in membranes prepared from cultured rat aortic smooth muscle cells. No binding proteins were identified in the kidney cortex, heart, adrenal capsule, adrenal medulla, peri-aortic brown adipose tissue, uterus or pituitary. Binding of renin to mesenteric artery membranes was prevented by inhibitors of renin enzymatic activity (H-77 and SQ 30697); this effect of H-77 showed a dose-dependence parallel to the inhibition of renin activity by this compound, suggesting that the binding of H-77 to the active site of renin prevents its binding to the membranes. CONCLUSIONS: These studies provide evidence for a vascular renin-binding mechanism, which may play a role in the generation of angiotensin peptides in vasculature, and may thus be a determinant of blood pressure. Moreover, one of the actions of inhibitors of renin enzymatic activity in vivo may be to prevent the binding of renin to the vasculature.

Angiotensinogen↗

PubMed1989

Effect of mineralocorticoids and salt loading on renin release, renal renin content and renal renin mRNA in mice.

1. DOCA and 9 alpha-fludrocortisone were given to mice on a high-sodium diet for periods of up to 20 weeks, resulting in decreases in plasma renin concentration, renal renin concentration and renal renin mRNA with both treatments. 2. Plasma renin concentration was suppressed prior to suppression of renin mRNA and renal renin levels, indicating that suppression of synthesis and secretion of renin occur separately. 3. The decrease in renal renin concentration that occurred with DOCA was greater and more rapid than the decrease that occurred with 9 alpha-fludrocortisone, suggesting that DOCA caused intra-renal breakdown of renin. 4. When DOCA was given to mice on a low-sodium diet, plasma renin concentration and renal renin concentration increased, indicating that the effects of DOCA on renin levels were dependent on dietary sodium. 5. Renin secretion and synthesis appeared to be controlled by different mechanisms and sodium balance has an important effect on both processes.

Animals↗

PubMed1989

Effects of renin inhibitors on the expression of kidney renin gene and tissue renin-like activity.

The effect of renin inhibitor ES-1005 on renin gene expression was investigated in sodium-depleted marmosets. The kidneys were removed after continuous infusion of ES-1005 (12 mg/kg per h) for 2 h. The relative amount of kidney renin messenger (m)RNA was measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin complementary (c)DNA fragment as a hybridization probe. Plasma renin activity was completely inhibited by ES-1005. The level of kidney renin mRNA decreased significantly to about one-third of the normal control value. We also investigated the inhibitory potency of the renin inhibitor ES-6864 on the renin-like activity in dog tissues (adrenal glands, aorta and brainstem). ES-6864 inhibited the tissue renin-like activity with an IC50 of 10(-7) to 10(-8) mol/l in vitro. Renin inhibitors not only inhibit the activity of plasma and tissue renin, but also suppress the synthesis of renin in the kidney.

Animals↗

PubMed2003

Dual renin-angiotensin system blockade restores blood pressure-renin dependency in individuals with low renin concentrations.

BACKGROUND: The prevailing sodium intake and renin-angiotensin system status influence the blood pressure response to an angiotensin II type 1 (AT1) receptor antagonist or an angiotensin I converting enzyme inhibitor, which is known to be reinforced by a low sodium intake or administration of a diuretic. OBJECTIVE: To investigate the possibility that combining both drugs might be more effective in conditions of high sodium intake than blocking the renin-angiotensin system in a single step. METHODS: In a placebo-controlled, four-period crossover study in 12 normotensive volunteers who received a high sodium chloride intake (more than 250 mmol/day for 6 days), the haemodynamic and renin effects of a single oral dose of irbesartan 150 mg combined with fosinopril 20 mg were compared with those of a usual daily dose of fosinopril (20 mg) and a high dose of irbesartan (300 mg). RESULTS: The changes in blood pressure induced by fosinopril and irbesartan alone were not different from those of placebo, whereas the combination significantly decreased blood pressure. Simultaneously, it increased plasma active renin and prorenin concentrations to a greater extent than did each single-site blocker. CONCLUSION: In low-renin conditions, combined renin-angiotensin system blockade enables the demonstration of a persistent renin-dependency of the blood pressure. Through its more efficient blockade of the renin-angiotensin system, demonstrated by the increase in renin and prorenin, combined renin-angiotensin system blockade is more effective than doubling the usual dose of an AT1 receptor antagonist. This may offer an alternative strategy for treating patients with a range of renin concentrations, and may potentially increase the cardio- and nephrotective benefits through a more complete blockade of the renin-angiotensin system.

Adolescent↗

PubMed1988

Similarity between active and trypsin-activated inactive renin in dog plasma by means of renin inhibition: the dog as an animal model for studies of inactive renin.

A method for trypsin-activation of dog plasma inactive renin is described. Liquid phase trypsin (final concentration 6.7 mg/ml) was used and the reaction was stopped after 2 min at 4 degrees C by soybean trypsin inhibitor (13 mg/ml). Renin was measured as angiotensin I (Ang I) generation in trypsin-treated and untreated plasma using the antibody-trapping method, in the presence of excess ox renin substrate. The renin-like activity after trypsin was indeed due to renin, since Ang I generation in dog plasma before and after trypsin treatment was completely inhibited by H-77 at 10(-6) mol/l, and the two IC50 values were very similar (2.7 +/- 0.7 and 2.9 +/- 0.7 at 10(-8) mol/l, respectively). Dog plasma inactive renin was effectively separated from active renin by chromatography on Affigel Blue. Like human prorenin, dog plasma inactive renin rose in response to sodium depletion (furosemide 5 mg/kg, i.v.) followed by a low-salt diet (1 mmol Na+/day) for 4 days, (from 29.6 +/- 8 to 162 +/- 22 microU/ml; P less than 0.01, n = 10). Active renin also increased as expected. Intravenous captopril (6 mg/kg per h), for 3 h, led to a sharp increase in dog plasma active renin (from 53 +/- 8 to 360 +/- 60 microU/ml; P less than 0.01, n = 6), whereas inactive renin remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1990

Response of plasma immunoreactive active renin, inactive renin, plasma renin activity, and aldosterone to hemodialysis in patients with diabetic nephropathy.

Several alterations in plasma active renin, inactive renin (prorenin), and aldosterone have been described in patients with diabetes mellitus. Such changes could be of some importance for patients on hemodialysis treatment, who must undergo severe changes in fluid and electrolyte status during each dialysis session. Therefore we studied the response of renin and aldosterone to hemodialysis in uremic diabetic nephropathy patients, using direct immunometric assays to measure plasma active renin concentration (ARC), inactive renin concentration (IRC), total renin concentration (TRC), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) in 11 male patients aged 39-69 (mean 53 +/- 2) with diabetic nephropathy and 11 male age-matched non-diabetics who had been on maintenance hemodialysis for 1-10 years. Although baseline values of IRC were slightly higher, and values of PAC lower in diabetics compared to non-diabetics, the results did not reach statistical significance. During hemodialysis, significant increases in ARC (p less than 0.01), TRC (p less than 0.05), and PRA (p less than 0.01), and a significant decrease (p less than 0.05) in PAC were seen in non-diabetic patients but no significant changes were observed in patients with diabetic nephropathy. IRC did not change during hemodialysis in either group of patients. There were no significant differences in body weight, blood pressure, or electrolyte changes in the two groups. These results suggest an altered response of plasma renin and aldosterone to hemodialysis in patients with diabetic nephropathy compared to non-diabetics. The reduced renin response could not be explained by a defect in conversion from inactive renin, but may be caused by decreased secretion of active renin in these patients.

Adult↗

PubMed1992

Assessment of the renin-angiotensin system in cirrhotic patients. Comparison between plasma renin activity and direct measurement of immunoreactive renin.

The renin-angiotensin system plays an important physiological role and has prognostic significance in cirrhotics with ascites. The degree of stimulation of this system is usually estimated by measuring plasma renin activity after incubation periods of 2-3 h. Recent investigations showed that the direct measurement of immunoreactive renin also estimates the degree of activity of the system. In this study, immunoreactive renin and plasma renin activity (measured at incubation periods of 10, 20, 50 and 180 min) were determined in ten healthy subjects, five hyperreninemic non-hepatic patients and 47 cirrhotics with ascites. Cirrhotic patients showed significantly higher plasma renin activity (5.1 +/- 0.9 ng/ml per h, p less than 0.05) and immunoreactive renin (145.4 +/- 24.4 pg/ml, p less than 0.01) than healthy subjects (1.2 +/- 0.15 ng/ml per h and 25.1 +/- 1.1 pg/ml, respectively). The angiotensin I generation rate was constant during the 3-h incubation in 22 cirrhotics and a close relationship (r = 0.956, p less than 0.001) between plasma renin activity (3.5 +/- 1.6 ng/ml per h) and immunoreactive renin (71 +/- 25 pg/ml) was observed in these patients. In the remaining 25 cirrhotics the generation rate of angiotensin I declined with time and the calculated plasma renin activity at 180 min was lower than the activity calculated at 10 min by 50.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1996

Clinical validation of renin monoclonal antibody-based sandwich assays of renin and prorenin, and use of renin inhibitor to enhance prorenin immunoreactivity.

Newly developed IRMAs to measure the plasma concentrations of renin and prorenin were validated for clinical use and compared with a classical enzyme kinetic assay. The IRMAs involve two monoclonal antibodies, one that reacts equally well with renin and prorenin and one that recognizes renin well but prorenin only minimally. Prorenin reactivity with the second antibody was enhanced by adding the renin inhibitor, Remikiren, to plasma. The complex of prorenin with this active-site ligand undergoes a conformational change, whereby prorenin is converted into a form that cannot be differentiated from renin by the IRMA. The linear working range of the assay was 4.0-3000 mU/L. The concentration of prorenin was calculated by subtracting the assay result obtained without Remikiren (i.e., renin) from the result obtained with Remikiren (i.e., renin plus prorenin). No more than 2% of prorenin present in plasma was detected as renin. The interassay CVs for renin quantification were 18%, 13%, and 8% at low, medium, and high concentrations, respectively. The interassay CV for calculated prorenin was 8% at both low and high concentrations. The IRMA results were highly correlated with those of an enzyme kinetic assay in healthy subjects; in patients with such conditions as primary hyperaldosteronism, renovascular hypertension, and low-, medium-, and high-renin essential hypertension; and in women undergoing gonadotropin stimulation.

Adult↗

PubMed1992

Modulation of active renin secretion by renin-binding protein (RnBP) in mouse pituitary AtT-20 cells transfected with human renin and RnBP cDNAs.

To investigate the role of renin-binding protein (RnBP) in renin metabolism, RnBP expression plasmid, which was constructed to express human RnBP under the control of mouse mammary tumor virus long terminal repeat, was transfected into mouse pituitary AtT-20 cells together with the expression plasmid encoding human renin. The transfectant secreted prorenin and active renin, whereas RnBP was expressed only in the presence of dexamethasone and without secretion into the medium. The secretion of active renin was stimulated by forskolin, and the stimulation was repressed by dexamethasone. The secretion of prorenin, however, was insensitive to forskolin irrespective of the presence or absence of dexamethasone. Moreover, the forskolin-stimulated release of active renin was hardly repressed by dexamethasone in AtT-20 cells transfected with the renin expression plasmid and a selectable plasmid pMAMneo. Coexistence of RnBP and renin mRNAs in human Wilms' tumor G-401 cells was shown by means of polymerase chain reaction of respective cDNAs from the cells. These results suggest that RnBP modulates the release of active renin in renin-producing cells.

Animals↗

PubMed1983

Reexamination of the effect of urinary kallikrein on renin release: evidence that kallikrein does not release renin but protects renin from destruction.

Previously, we showed that superfusion of rat kidney slices by rat urinary kallikrein stimulated renin release. The resin measurements were performed on superfusion samples which we stored frozen at -20 C for 24 h. In this study we investigated the effect of freezing on the renin concentration of superfusion samples in the control period. The renin concentration measured immediately without freezing was 9.8 +/- 2.4 ng angiotensin I/10 ml . 3 h/mg tissue, while the concentration in the samples frozen for 24 h was 2.9 +/- 1.0 ng angiotensin I/10 ml . 3 h/mg. The renin concentration of the superfusion samples during the kallikrein perfusion period was the same as that of the nonfrozen control samples. It appeared, therefore, that kallikrein acted as if it stimulated renin release from kidney slices, when the renin was measured in frozen samples. To clarify this phenomenon, we added kallikrein, inactivated kallikrein, and albumin to superfusion samples of the control period and froze the samples for 24 h. After freezing, the renin concentration of the control samples decreased to about 20% of that of nonfrozen samples, except in those samples to which the various proteins were added. In these samples, the loss of renin activity was prevented. The addition of Trasylol, a specific inhibitor of kallikrein, blocked the protective effect of both kallikrein and albumin. These data suggest that the renin released into the superfusion media of kidney slices is destroyed by freezing and that kallikrein or BSA prevents this destruction. These data negate previous data indicating that kallikrein stimulates renin release.

Animals↗