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Biomedical subjects

J E Sealey

Publications and source records attributed to J E Sealey.

At least 37 records · Page 2Linked to original sources
PubMed1996

Chronic carvedilol reduces mortality and renal damage in hypertensive stroke-prone rats.

The effects of carvedilol, a novel vasodilating beta-blocker and antioxidant, and propranolol on survival, neurobehavioral deficits, cardiovascular parameters, plasma renin, plasma aldosterone levels and renal pathology were determined in stroke-prone spontaneously hypertensive rats. Stroke-prone spontaneously hypertensive rats were allowed access to 1% NaCl as the drinking solution and a high fat diet supplemented with carvedilol (1200 or 2400 ppm) or propranolol (2400 ppm). The control group consisted of stroke-prone spontaneously hypertensive rats placed on the same diet with no drug supplement. Animals fed propranolol had a blood level of 864 +/- 68 ng/ml, whereas carvedilol-fed animals had blood levels of 24 +/- 4 ng/ml at 1200 ppm and 471 +/- 145 ng/ml at 2400 ppm. Carvedilol and propranolol treatment resulted in significant beta adrenoceptor blockade. Both compounds reduced heart rate, but had no significant effects on systolic arterial blood pressure. Carvedilol- and propranolol-treated animals also exhibited significant, prolonged protection from neurobehavioral deficits and mortality (P < .01). Elevated plasma renin activity and aldosterone levels seen in untreated controls were significantly decreased by propranolol (P < .05), and to a considerably greater extent by the same dose of carvedilol (P < .01). Carvedilol decreased renal histopathological damage and cardiac hypertrophy to a greater extent (P < .01) than propranolol (at equal doses). Both carvedilol (P < .01)- and propranolol (P < .01)-treated animals had considerably reduced renal damage at 18 weeks of treatment. Carvedilol reduced renal damage more than propranolol (P < .05). In addition, the lower (1200 ppm) dose of carvedilol, which decreased neurobehavioral deficits and mortality, had no significant effects on organ mass or renal function, but significantly (P < .01) reduced renal damage. These data indicate that both beta adrenoceptor blockers, especially carvedilol to a considerably greater degree, convey significant protection in a genetic model of severe hypertension that results in renal and cardiovascular organ pathology, neurobehavioral deficits and premature death.

Adrenergic beta-Antagonists↗
PubMed1995

Role of renin-angiotensin system in blood pressure regulation in pregnancy.

We gave captopril (25 mg) to nine pregnant and eight non-pregnant women. From baseline to 60 min post-captopril, mean arterial pressure decreased significantly more in pregnant than in non-pregnant women (mean 15.0 [SE 2.5] vs 5.2 [1.2] mm Hg; difference 9.8 [95% CI 3.9-15.9] mm Hg, p = 0.0036), whereas plasma renin activity increased significantly more in the pregnant group (18.0 [5.5] vs 4.5 [1.9] ng mL-1 h-1; difference 13.5 [0.71-26.5], p = 0.043). These findings support the hypothesis that stimulation of the renin-angiotensin system in pregnancy maintains blood pressure.

Adult↗
PubMed1995

Serum sex hormone levels and renin-sodium profile in men with hypertension.

Both a high renin-sodium profile and abnormal levels of sex hormones have been linked to myocardial infarction (MI) in men. The present study was carried out in men with hypertension to determine whether renin-sodium profile and sex hormone levels are related to each other. Renin-sodium profile, estradiol, testosterone, sex-hormone binding globulin (SHBG), and risk factors for MI, ie, cholesterol, insulin, glucose, and blood pressure, were determined in 45 men with hypertension. The mean serum estradiol level of the 13 men with high renin profile (30.1 +/- 6.5 pg/mL) was significantly higher (P = .01) than that of the nine men with low renin profile (22.6 +/- 3.9), while the mean level of the 23 men with normal renin profile was intermediate (26.2 +/- 5.3). The levels of estradiol and plasma renin activity correlated in the 45 patients before (r = 0.48, P = .001) and after (r = 0.46, P = .002) controlling for age. The mean estradiol-to-testosterone ratio was also higher (P = .04) and the mean SHBG level lower (P < .02) in the high renin group, but the mean testosterone level was not significantly different between the high and low renin groups. Although none of the risk factors was significantly different between the high and low renin groups, all of the mean values in the high renin group were in the direction of increased MI risk. These findings suggest that in men with hypertension, renin profile may be related to estradiol level and possibly to risk factors for MI.

Blood Glucose↗
PubMed1995

Low urinary sodium is associated with greater risk of myocardial infarction among treated hypertensive men.

A sodium-reduced diet is frequently recommended for hypertensive individuals. To determine the relationship of sodium intake to subsequent cardiovascular disease, we assessed the experience of participants in a worksite-based cohort of hypertensive subjects. The 24-hour urinary excretion of sodium (UNaV), potassium, creatinine, and plasma renin activity was measured in 2937 mildly and moderately hypertensive subjects who were unmedicated for at least 3-4 weeks. Morbidity and mortality in these systematically treated subjects were ascertained. Men and women were stratified according to sex-specific quartiles of UNaV. Subjects in these strata were similar in race, cardiovascular status, and pretreatment and intreatment blood pressure. Subjects with lower UNaV were thinner, excreted less potassium, and had higher plasma renin activity. During an average 3.8 years of follow-up, a total of 55 myocardial infarctions occurred. Myocardial infarction and UNaV were inversely associated in the total population and in men but not in women, who sustained only nine events. In men, age- and race-adjusted myocardial infarction incidence in the lowest versus highest UNaV quartile was 11.5 versus 2.5 (relative risk, 4.3, 95% confidence interval, 1.7-10.6). No association was observed between non-cardiovascular disease mortality (n = 11) and UNaV. There was a significant linear trend in proportions of myocardial infarction by UNaV quartile, with a break point after the lowest UNaV quartile.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Evidence for cardiovascular effects of prorenin.

This report investigates whether there is evidence that prorenin has cardiovascular effects. The report concludes that prorenin may indeed have cardiovascular effects, causing regional vasodilation by counteracting the vasoconstrictor effect of renin, and thereby maintaining blood flow to vital organs. This view is based on several observations. In direct contrast to renin, high levels of prorenin are not associated with vasoconstriction. (1) Prorenin is expressed almost exclusively in tissues with extraordinarily high levels of blood flow: pregnant uterus, placenta, ovaries, kidneys, eyes. (2) In the ovaries, the higher the prorenin level the higher the level of steroid biosynthesis, consistent with a increased tissue perfusion or metabolism. (3) Blood pressure gradually falls when prorenin is infused into monkeys, even when the source of prorenin is contaminated with renin which should increase blood pressure. (4) Prorenin levels positively correlate with renal blood flow under several experimental conditions. (5) Salt sensitivity of blood pressure, a renal vasoconstricted state, is associated with subnormal prorenin levels. (6) Diabetes mellitus and pregnancy, two vasodilated states, are associated with high plasma prorenin levels. (7) Prorenin binds to a membrane receptor that also recognizes renin. Thus, prorenin could vasodilate by competing with the specific uptake of renin and thereby reduce the level of regional vasoconstriction. Altogether, the cardiovascular haemodynamic setting associated with high levels of prorenin is the opposite of that associated with high levels of renin and is consistent with a vasodilator effect in the kidneys and reproductive organs and perhaps elsewhere.

Animals↗
PubMed1995

Angiotensinogen depletion by high renin levels in hypertensive rats: no evidence for tonic stimulation of angiotensinogen by angiotensin II.

OBJECTIVE: Data concerning the effect of angiotensin II (Ang II) on plasma angiotensinogen levels are conflicting. Although Ang II is reported to stimulate the biosynthesis of angiotensinogen, plasma angiotensinogen is often depleted by renin when the level of renin, and therefore Ang II, increases. In the present study we used the Ang II subtype 1 (AT1) receptor antagonist losartan to investigate whether rising plasma Ang II levels stimulate angiotensinogen production to counteract the falling plasma angiotensinogen levels caused by increasing renin activity in plasma. METHOD: Angiotensinogen was measured in plasma from two previously reported studies in which 6-week-old stroke-prone spontaneously hypertensive rats (SHRSP) or Dahl salt-sensitive (Dahl-S) rats were fed high-salt diets (4 and 8% sodium chloride, respectively) for 10-12 weeks with or without losartan. RESULTS: As reported previously, plasma renin was suppressed during the first 4 weeks of the high-salt diet but then paradoxically increased in both strains. When plasma renin increased, plasma angiotensinogen levels fell to 45 and 62% of the baseline value. The plasma renin concentration was negatively correlated with plasma angiotensinogen both in SHRSP and in Dahl-S rats (r = -0.76, P < 0.001 and r = -0.60, P < 0.001, respectively). In Dahl-S rats losartan treatment was associated with lower levels of plasma angiotensinogen but caused greater increases in plasma renin. When differences in renin were taken into account, plasma angiotensinogen levels were not different in losartan-treated and untreated Dahl-S rats. Similarly to Dahl-S rats, plasma angiotensinogen fell in SHRSP when renin increased, but SHRSP had higher plasma angiotensinogen levels during losartan treatment because plasma renin concentration was lower. CONCLUSION: The present study shows, in two strains of hypertensive rat, that an increase in plasma renin levels is associated with a fall in plasma angiotensinogen levels. Concurrent treatment with an Ang II AT1 receptor antagonist does not augment this fall, except to the extent that renin rises further. The results provide no evidence for a significant tonic stimulatory effect of Ang II on plasma angiotensinogen levels.

Administration, Oral↗
PubMed1995

Midwall left ventricular performance in salt-loaded Dahl rats: effect of AT1 angiotensin II inhibition.

OBJECTIVE: The relationship between left ventricular midwall shortening and circumferential end-systolic stress was studied in Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats after 6-8 weeks of an 8% Na+ diet with or without losartan, an AT1 angiotensin II receptor antagonist. MATERIALS AND METHODS: Losartan was given in drinking water to 13 Dahl S and 13 Dahl R rats, while 14 control Dahl S and 14 control Dahl R rats were given tap water, for 8 weeks. The endpoint was the last blood pressure and echocardiographic examination after 8 weeks or before death for rats which did not survive the entire period. Tail blood pressure was measured in awake animals and two-dimensional guided M-mode echocardiography was used. RESULTS: The left ventricular midwall shortening-circumferential end-systolic stress relationship in 45 normotensive Wistar rats was used to calculate the ratio of observed to predicted left ventricular midwall fractional shortening. At the endpoint, afterload-independent midwall shortening was higher in Dahl S rats on losartan or tap water, and in Dahl R rats on losartan than in weight-matched normotensive Wistar rats (all P<0.05). Afterload-independent midwall shortening was related to the left ventricular chamber dimension in a learning series of 109 rats (64 Goldblatt and 45 normotensive rats on a normal sodium diet; r = 0.73) and was adjusted in Dahl rats to a constant left ventricular internal diameter (6.9 mm) by the learning regression equation. The adjusted afterload-independent midwall shortening was still higher in Dahl S rats on losartan than in controls (P<0.02). Left ventricular internal diameter-adjusted afterload-independent midwall shortening was inversely related to the left ventricular mass in both Dahl S and Dahl R groups (r = -0.40 and -0.72, both P<0.04). CONCLUSIONS: (1) Midwall left ventricular performance was higher in Dahl S than Dahl R rats on a high-salt diet; (2) this elevation was partially independent of an increase in left ventricular chamber size, an indirect measure of preload; and (3) in Dahl S rats on losartan, increased left ventricular performance is related to improved contractility, associated with a blunted development of left ventricular hypertrophy.

Angiotensin Receptor Antagonists↗
PubMed1994

Diagnosis and treatment of primary hyperaldosteronism.

OBJECTIVE: To characterize the clinical and laboratory features of primary aldosteronism and to evaluate which diagnostic tests can discriminate surgically curable forms of this syndrome. DESIGN: Retrospective analysis of the following data from 82 patients with primary aldosteronism: blood pressure, serum electrolytes, urinary aldosterone and electrolytes, computed tomographic scans, plasma renin and aldosterone before and during upright posture, atrial natriuretic peptide, and adrenal vein aldosterone and cortisol. Clinical outcomes assessed after treatment included blood pressure, serum electrolytes, and plasma renin activity. RESULTS: Drug therapy was discontinued before diagnostic tests were done in 56 of 82 patients (34 with adenomas and 22 with hyperplasia). Compared with patients with hyperplasia, those with adenomas had higher systolic (184 mm Hg and 161 mm Hg, respectively; P < 0.001) and diastolic blood pressures (112 mm Hg and 105 mm Hg; P = 0.03), lower serum potassium levels (3.0 mmol/L and 3.5 mmol/L; P < 0.001), and higher serum CO2 (P = 0.001), atrial natriuretic peptide (P = 0.008), and urinary 18-methyl oxygenated cortisol metabolite levels (P = 0.02). In patients with adenomas, aldosterone secretion lateralized to one adrenal gland and did not increase during the postural stimulation test; preoperative urinary aldosterone levels were correlated with diastolic pressures (r = 0.58; P = 0.001). Hypertension was "cured" postoperatively in approximately 35% of patients with adenomas and those with hyperplasia (P > 0.2) but was "improved" more frequently in those with adenomas (P = 0.002). Cured patients from both groups were younger than those not cured (mean ages, 43 years and 54 years, respectively; P = 0.002) and had lower preoperative mean plasma renin activity (0.17 ng/mL per hour and 0.50 ng/mL per hour; P < 0.001). All patients with adenomas in whom aldosterone secretion lateralized were either cured or improved. CONCLUSION: Of the 51 patients with primary aldosteronism who had adrenalectomy (43 patients with adenomas and 8 with hyperplasia), those most likely to be cured were younger and had lower plasma renin activity. In patients with adenomas who were cured or improved, aldosterone secretion was more likely to lateralize. Tests that distinguished adenomas from adrenal hyperplasia included the postural stimulation test, urinary excretion rates of 18-oxocortisol and 18-hydroxycortisol, and adrenal vein sampling.

Adenoma↗
PubMed1994

Angiotensinogen dependency of blood pressure in two high-renin hypertensive rat models.

In this analysis we investigated whether angiotensinogen (Aogn) levels were related to blood pressure (BP) in two hypertensive rat models when renin secretion was either under physiologic regulation or out of control. These relationships were investigated using BP data from previous reports in which SHRsp and Dahl S rats were studied for 10 to 12 weeks while ingesting a high-salt diet with and without the angiotensin II (AngII) antagonist losartan. During the first 4 weeks of high-salt diet, plasma renin concentration (PRC) was appropriately suppressed but it subsequently increased paradoxically in both strains. During the first 4 weeks, when renin secretion was under normal control, as indicated by its suppression by the high-salt diet and by an inverse relationship between PRC and BP (r = -0.69, P < .001 and r = -0.53, P < .01 in Dahl S and SHRsp, respectively), there was no relationship between BP and plasma Aogn. In contrast, when renin secretion increased paradoxically, the inverse relationship between BP and PRC was lost and a positive relationship was found between BP and plasma Aogn in both Dahl S rats (r = 0.70, P < .01) and SHRsp (r = 0.57, P < .01). There was no relationship between BP and Aogn in either strain during treatment with losartan either before or after 4 to 6 weeks of salt feeding. These results show Aogn dependency of BP, but only under conditions in which renin cannot feed back normally. The Aogn relationship to BP was most likely dependent on the vasoconstrictor effect of AngII since it was lost during AngII AT1 receptor antagonism.

Angiotensin II↗
PubMed1994

Renin is not synthesized by cardiac and extrarenal vascular tissues. A review of experimental evidence.

A comprehensive review of physiological and molecular biological evidence refutes claims for synthesis of renin by cardiac and vascular tissues. Cardiovascular tissue renin completely disappears after binephrectomy. Residual putative reninlike activity, where investigated, has had the characteristics of lysosomal acid proteases. Occasional reports of renin or renin mRNA in vascular and cardiac tissues can be ascribed to failure to remove the kidneys 24 hours beforehand, overloading of detection systems, problems with stringency in identification, and illegitimate transcripts after more than 25 cycles of polymerase chain reaction. Others, using more stringent criteria, have failed to detect cardiac and vascular renin mRNA. Accordingly, a growing number of investigators have concluded that the kidneys are the only source of cardiovascular tissue renin. Although prorenin is secreted from extrarenal tissues as well as from the kidneys, there is no evidence that it is ever converted to renin in the circulation. The kidney is the only tissue with known capacity to convert prorenin to renin and to secrete active renin into the circulation. Accordingly, renin of renal origin determines plasma and hence, extracellular fluid renin levels. In these loci, angiotensin (Ang) I, formed by renin cleavage of circulating and interstitial fluid angiotensinogen, is in turn cleaved by angiotensin converting enzyme, located in plasma and extracellular fluids and on the luminal surface of pulmonary and systemic vascular endothelial cells, to Ang II, which perfuses and bathes the heart and vasculature. Consistent with this model, plasma renin and angiotensin and the antihypertensive action of renin inhibitors, converting enzyme inhibitor, or Ang II antagonists all disappear after binephrectomy. Thus, the plasma renin level, via Ang II formation, determines renin system vasoconstrictor activity, the antihypertensive potential of anti-renin system drugs, and the risk of heart attack in hypertensive patients. This analysis redirects renin research to renal mechanisms that create the plasma renin level, to renal prorenin biosynthesis and its processing to renin, and to their regulated secretion, extracellular distribution, and possible binding to by target tissues. In this context, it is still possible that changes in circulating and interstitial renin substrate or available converting enzyme might exert subtle modulating influences on Ang II formation. However, this analysis redefines the importance of plasma renin measurements to assess clinical situations, because plasma renin is the only known initiator driving the cardiovascular renin-angiotensin system, and its strength can be measured.

Angiotensin I↗
PubMed1994

Estradiol- and progesterone-related increases in the renin-aldosterone system: studies during ovarian stimulation and early pregnancy.

To investigate the degree to which endogenous increases in estradiol (E2) and progesterone (P4) are associated with changes in the renin system, we studied eight patients undergoing ovarian stimulation for in vitro fertilization (FSH/human menopausal gonadotropin or clomiphene citrate for 5-11 days, followed by hCG). Three conceived and were followed for up to 62 days after hCG treatment. The others were followed until the end of the luteal phase. During the follicular phase, E2 increased 10-fold, PRA increased 2-fold, and absolute levels of E2 and P4 were positively correlated (r = 0.63; P < 0.05). After ovulation, which was induced by hCG, E2 fell by 50% (day 7), but there was a 50-fold increase in P4 and a further 5-fold increase in PRA. By day 14, E2 increased again in the women who conceived, to levels even higher than those in the follicular phase, and both P4 and PRA increased 2- to 3-fold between days 7 and 14. In contrast, E2, P4, and PRA returned toward baseline levels in the nonpregnant women. On day 21, E2, P4, and PRA remained very high in the pregnant women [E2, 2297 +/- 255 pg/mL (8430 pmol/L); P4, 103 +/- 22 pg/mL (328 pmol/L); PRA, 33 +/- 8 ng/mL.h (9.17 ng/L.s)]. During the luteal phase and early pregnancy, there was a positive relationship between PRA and P4 (r = 0.68; P < 0.05). There was also a positive relationship between PRA and E2 (r = 0.54; P < 0.05); compared to the follicular phase level, PRA was 4-fold higher in the luteal phase at any E2 level. Like renin, urinary aldosterone excretion (UA) increased 5-fold during the luteal phase (day 7) and by a further 3-fold between days 7 and 21 in the pregnant women, reaching very high levels [135 +/- 28 micrograms/day (375 nmol/day); n = 3]. PRA and UA positively correlated (r = 0.59; P < 0.08). Plasma angiotensinogen increased from 2146 +/- 283 ng angiotensin-I/mL (n = 8) to 3682 +/- 607 (n = 8) on day 7 and to 5353 +/- 799 (n = 3) on day 21. Urinary sodium excretion did not fall, and urinary potassium did not increase in coordination with the changes in renin and aldosterone. There was no hypokalemia. These results demonstrate marked increases in plasma renin and UA in coordination with increases in plasma E2 and P4 during ovarian stimulation and early pregnancy, and coordinated falls during luteolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Response to the captopril test is dependent on baseline renin profile.

OBJECTIVE: To determine prospectively the relationship between the renin-sodium profile and the renin response to captopril challenge in patients with essential hypertension. DESIGN: A standard captopril test was performed in 108 uncomplicated, untreated hypertensive subjects with normal renal function and urinary sodium excretion in the range 50-240 mmol/day. The subjects were selected from a working population with a low expected prevalence of renovascular disease. METHOD: The captopril test was considered positive if the captopril-induced rise in plasma renin activity met all three criteria established by Müller et al. Patients with a positive test and those meeting only one or two of the three criteria were further investigated for renovascular hypertension by measuring renal venous renins and by digital subtraction intravenous angiography. Renin responses were analyzed according to baseline renin-sodium profile. RESULTS: Nine of 108 subjects had a false-positive captopril test result. Among the subjects with a low or normal renin-sodium profile, 1% (one of 82) had a false-positive result. In contrast, false-positive results were seen in 31% (eight of 26) of high-renin subjects. False-positive test results were not related to urinary sodium excretion or to excessive decrease in blood pressure. The magnitude of the renin response to captopril was strongly and directly related to the baseline plasma renin activity. CONCLUSION: An exaggerated renin response to captopril challenge is common in patients with high-renin essential hypertension. Therefore, in a population with a low probability of renovascular hypertension, caution is recommended in interpreting a positive test result in patients with a high baseline renin.

Adult↗
PubMed1993

Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension.

OBJECTIVE AND DESIGN: It has been hypothesized that risk factors for coronary heart disease in men are linked and that the underlying factor linking them may be an alteration in the sex hormone milieu. As a test of this hypothesis, sex hormones and fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), hemostatic factors recently shown to be risk factors for myocardial infarction, were measured in men with hypertension and in healthy control subjects. RESULTS: The fasting serum testosterone and free testosterone levels were decreased and the plasma factor VII and PAI-1 levels increased in the men with hypertension. CONCLUSION: These findings are consistent with the stated hypothesis.

Blood Coagulation Factors↗
PubMed1993

Adrenergic regulation of renin secretion and renal hemodynamics during deliberate hypotension in humans.

To assess the relative contributions of neural and nonneural stimuli of renin secretion, the effects of an alpha 1-agonist, phenylephrine (Phe), or a beta-agonist, epinephrine (Epi), on plasma renin activity (PRA), renal blood flow (RBF), and glomerular filtration rate (GFR) were compared during sympathetic blockade with epidural hypotensive anesthesia [mean arterial blood pressure (MAP) = 60 and 50 mmHg]. Controls (NaCl) received saline alone to maintain MAP at 50 mmHg. Epi increased PRA (ng.ml-1.h-1) from 0.9 +/- 0.6 to 3.0 +/- 1.5 at 60 mmHg MAP and 4.7 +/- 1.8 at 50 mmHg MAP, with associated decreases in RBF (-33 and -60%, respectively) and GFR (-27 and -53%, respectively). During hypotension with Phe and NaCl, PRA and RBF were unchanged from baseline but GFR decreased. Urinary Na secretion decreased comparably in all three groups. In conclusion, during sympathetic blockade with epidural anesthesia, marked reductions in both renal perfusion pressure and distal nephron Na delivery were insufficient to increase renin secretion. beta-Adrenergic stimulation (e.g., Epi) was required to increase PRA. Epi decreased RBF suggesting an angiotensin II-mediated effect.

Anesthesia, Epidural↗
PubMed1992

Reversible cryoactivation of recombinant human prorenin.

Cleavage of prorenin's prosegment causes irreversible formation of renin. In contrast, renin activity is reversibly exposed when prorenin is acidified to pH 3.3. Nonetheless, acidification of plasma results in irreversible activation of prorenin, because endogenous proteases cleave the prosegment of acid-activated prorenin. Chilling of plasma results in irreversible cryoactivation of prorenin. In this study we investigated whether cryoactivation of purified prorenin is reversible. The intrinsic renin activity of recombinant human prorenin was measured by an enzyme kinetic assay using partially purified human angiotensinogen as substrate. Results are expressed as a percent (mean +/- S.E.) of the maximal activity exposed after limited proteolysis by trypsin. The intrinsic renin activity of two pools (0.3 and 0.06 Goldblatt units/ml) was 1.5% +/- 0.3 and 1.2% +/- 0.6 at 37 degrees C. Activity increased to 19% +/- 0.3 and 26% +/- 0.5 after incubation at 0 degrees C and to 5.4% +/- 0.5 and 2.1% +/- 1.2 at room temperature. Cryoactivation did not occur in buffers containing more than 1 M NaCl. It took 8 min at 37 degrees C or 180 min at room temperature for cryoactivated prorenin to lose half of its intrinsic renin activity. It took 48 and 26 h, respectively, at 0 degree C for the two pools of prorenin at 37 degrees C to regain half of their maximum intrinsic activity at 0 degrees C. A direct immunoradiometric assay that detects active renin but not prorenin was able to detect cryoactivated prorenin. These results show that human prorenin can be reversibly cryoactivated in buffers of low ionic strength and has greater intrinsic activity at room temperature than at 37 degrees C.

Catalysis↗