Plasma Renin Activity and Aldosterone Secretion in Hypertensive Patients During High and Low Sodium Intake and Administration of Diuretic1

The present study was carried out to procure detailed information on the relationship between chronic sodium restriction and renin content of kidneys at a subcellular level in the rat. Renin granules (RG) were separated by a discontinuous sucrose-density gradient (from 1.2 to 1.7 M) centrifugation. In control rats, RG were mainly recovered in the fractions corresponding to 1.5 M sucrose, whereas most of the mitochondria, lysosomes, and microsomes equilibrated in upper fractions. The RG fraction contained approximately 60% of total granular renin activity. Low sodium intake for 4 wk resulted in a 12.4-fold increase in plasma renin activity and led to a 2.6-fold increase in renin activity of the RG fraction. But in sodium-restricted rats there was no alteration in the distribution pattern of renin activity on sucrose-density gradients, indicating that there was no change in the density of RG. These results provide evidence for increased renin activity in storage granules following chronic sodium restriction.

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L-arginine analogues inhibit aldosterone secretion in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.5.r1137 ◽

1995 ◽

Vol 268 (5) ◽

pp. R1137-R1142 ◽

Cited By ~ 3

Author(s):

J. C. Simmons ◽

R. H. Freeman

Keyword(s):

Blood Flow ◽

Angiotensin Ii ◽

Methyl Ester ◽

Arterial Pressure ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Renin Activity ◽

Bilateral Nephrectomy ◽

Aldosterone Secretion ◽

Series Of Experiments

L-Arginine analogues, e.g., NG-nitro-L-arginine methyl ester (L-NAME), increase arterial pressure and suppress renin release in the rat. On the basis of these observations, it was hypothesized that L-arginine analogues also would attenuate aldosterone secretion. This hypothesis was tested in anesthetized rats treated with L-NAME or NG-nitro-L-arginine (L-NNA, 185 mumol/kg ip). The aldosterone secretion rate, plasma renin activity, and adrenal blood flow were attenuated in rats treated with L-NAME and L-NNA compared with control animals. Similar experiments were performed in anephric rats to examine the effects of L-NAME on aldosterone secretion independent of the circulating reninangiotensin system. The administration of L-NAME reduced adrenal blood flow but failed to reduce aldosterone secretion in these anephric rats. Bilateral nephrectomy reduced plasma renin activity essentially to undetectable levels in these animals. In a third series of experiments, two groups of anephric rats were infused with angiotensin II (3 micrograms/kg body wt iv) to provide a stimulus for aldosterone secretion. Aldosterone secretion and adrenal blood flow were markedly reduced in angiotensin II-infused rats pretreated with L-NAME compared with the control anephric animals infused with angiotensin II. Overall these results suggest that L-arginine analogues attenuate aldosterone secretion by inhibiting the adrenal steroidogenic effects of endogenous or exogenous angiotensin II and/or by reducing plasma levels of renin/angiotensin.

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Effect of temperature on plasma renin samples.

Clinical Chemistry ◽

10.1093/clinchem/24.7.1202 ◽

1978 ◽

Vol 24 (7) ◽

pp. 1202-1204 ◽

Cited By ~ 13

Author(s):

F Fyhrquist ◽

L Puutula

Keyword(s):

Plasma Renin Activity ◽

Room Temperature ◽

Plasma Renin ◽

Renin Activity ◽

Effect Of Temperature ◽

Plasma Samples ◽

Hypertensive Patients ◽

Variable Extent ◽

Venous Plasma

Abstract Plasma renin activity was measured in parallel in Na2EDTA-contained plasma samples after storage at -20, 4, and 24 degrees C, and in the lyophilized state. In peripheral venous plasma from 22 hypertensive patients, the activity (range, 0.08-46.7 microgram/liter per hour) remained stable during three days of storage at 4 degrees C, but decreased to a variable extent when plasma was kept at 24 degrees C: in one day by 9.2%, two days by 25.6%, and three days by 74.0%. Values were the same for samples handled at room temperature and chilled to 4 degrees C within 3 h and parallel samples immediately cooled in an icebath and kept at 4 degrees C. Freezing (-20 degrees C) and thawing of plasma was associated with a 22% mean increase in activity (range, 0-83%). Lyophilization resulted in a smaller increase of plasma renin activity (mean 12%, range 0-46%). Blood for renin analysis need not be cooled immediately, but must be cooled to 4 degrees C within 2-3 h. It then is stabe for at least three days. Freezing or lyophilization appears to be associated with some cold activation of "prorenin."

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Renal sodium handling in normal humans subjected to low, normal, and extremely high sodium supplies

AJP Renal Physiology ◽

10.1152/ajprenal.1985.249.6.f941 ◽

1985 ◽

Vol 249 (6) ◽

pp. F941-F947 ◽

Cited By ~ 8

Author(s):

J. C. Roos ◽

H. A. Koomans ◽

E. J. Dorhout Mees ◽

I. M. Delawi

Keyword(s):

Blood Pressure ◽

Plasma Renin Activity ◽

Sodium Intake ◽

Extracellular Fluid ◽

Plasma Renin ◽

Renin Activity ◽

Sodium Reabsorption ◽

Lithium Clearance ◽

Renal Sodium Handling ◽

Sodium Handling

We studied renal sodium handling, extracellular fluid volume (ECFV), plasma renin activity, aldosterone and norepinephrine, and blood pressure in eight healthy volunteers after equilibration on intakes of 20, 200, and 1,128 +/- 141 meq sodium, respectively. Renal sodium handling was assessed by means of clearance studies during maximal water diuresis and lithium clearance. Urinary sodium excretions were 22 +/- 4, 202 +/- 19, and 1,052 +/- 86 meq/day. From the lower to the upper sodium intake level, 24-h creatinine clearance rose from 111 +/- 7 to 136 +/- 11 ml/min and inulin clearance from 103 +/- 9 to 129 +/- 9 ml/min, whereas proximal and distal fractional sodium reabsorption (FSRprox and FSRdist, respectively) fell from 86.8 +/- 1.3 to 79.0 +/- 2.7% and from 96.5 +/- 0.5 to 76.0 +/- 1.9%, respectively. During the normal sodium intake (200 meq), intermediate values were recorded. The changes in fractional lithium clearance were less consistent but correlated with FSRprox (r = 0.78, P less than 0.001) and not with FSRdist. Major changes in plasma renin activity, aldosterone, and, to a lesser extent, norepinephrine accompanied these changes in kidney function, displaying inverse and exponential correlations with daily sodium excretion and ECFV. No consistent rise in blood pressure was detected. These observations indicate that in healthy humans renal adaptation to vast variations in sodium intake includes resetting of glomerular filtration rate, FSRprox, and, in particular, FSRdist. Alterations in neurohumoral factors may play a dominant role in this adaptation.

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Plasma renin activity and plasma prorenin assays

Clinical Chemistry ◽

10.1093/clinchem/37.10.1811 ◽

1991 ◽

Vol 37 (10) ◽

pp. 1811-1819 ◽

Cited By ~ 139

Author(s):

J E Sealey

Keyword(s):

Plasma Renin Activity ◽

Sodium Intake ◽

Vascular Complications ◽

Plasma Renin ◽

Renin Activity ◽

Blood Collection ◽

Kinetic Assay ◽

Renin Substrate ◽

Patients With Diabetes ◽

Commercial Kits

Abstract Sensitivity and accuracy are essential features of an assay of plasma renin activity (PRA) because the normal concentration of PRA is only 1 pmol/L, and subnormal concentrations have diagnostic relevance. Conditions for blood collection need to be standardized but the conditions are not difficult for outpatients. For routine diagnostic purposes blood should be collected from ambulatory (ideally, untreated) patients on moderate sodium intake. To avoid irreversible cryoactivation of plasma prorenin (which is present in 10-fold greater concentrations than renin), samples should be processed at room temperature and stored completely frozen. Cryoactivation occurs when plasma is liquid at temperatures less than 6 degrees C. PRA is commonly measured with an enzyme kinetic assay in which angiotensin I (Ang I) is formed by the reaction of plasma renin with endogenous renin substrate (angiotensinogen). The Ang I so formed is measured by RIA; results are expressed as an hourly rate (micrograms/L formed per hour). This method, which is provided by most commercial kits, has the potential for unlimited sensitivity because the step for Ang I generation can be prolonged as long as necessary, so that enough Ang I forms to be measured accurately. Unfortunately, that sensitivity is not always exploited. Dilution of plasma during pH adjustment should be kept to a minimum. The Ang I generation step should last at least 3 h. The step should last 18 h for samples with PRA less than 1.0 micrograms/L per hour, to eliminate the errors inherent in the measurement and subtraction of immunoreactive Ang I in the untreated plasma (blank subtraction). These changes actually simplify PRA measurements because they eliminate the need for ice in the clinic and reduce by almost half the number of samples to be assayed by RIA. I also describe the method for measurement of plasma prorenin, which may be an important marker for patients with diabetes mellitus who subsequently develop vascular complications.

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Development of two-kidney Goldblatt hypertension in rats under dietary sodium restriction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1980.238.6.h889 ◽

1980 ◽

Vol 238 (6) ◽

pp. H889-H894 ◽

Cited By ~ 3

Author(s):

H. Munoz-Ramirez ◽

R. E. Chatelain ◽

F. M. Bumpus ◽

P. A. Khairallah

Keyword(s):

Blood Pressure ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Renin Activity ◽

Dietary Sodium ◽

Sodium Restriction ◽

Sodium Diet ◽

Low Sodium Diet ◽

Low Sodium ◽

Goldblatt Hypertension

In Sprague-Dawley rats with unilateral renal artery stenosis and an intact contralateral kidney, administration of a low-sodium diet did not prevent the development of hypertension. Despite an elevated blood pressure, hyponatremia, marked activation of the renin-angiotensin system, and increased hematocrit values, only 10% of the rats showed lesions of malignant hypertension. Systolic blood pressures of one- and two-kidney sham-operated rats fed a low-sodium diet were significantly higher than that of normotensive controls fed a normal diet. Uninephrectomy did not reduce plasma renin activity. The low-sodium diet increased plasma renin activity to about the same level in one- and two-kidney normotensive rats. However, the increase in plasma renin activity elicited by dietary sodium restriction was markedly less in one-kidney Goldblatt hypertension. Systolic blood pressure reached similar levels in one- and two-kidney Goldblatt hypertensive rats fed a low-sodium diet. These data indicate that a decrease in sodium intake does not prevent the development of two-kidney Goldblatt hypertension.

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Activity Assays and Immunoassays for Plasma Renin and Prorenin: Information Provided and Precautions Necessary for Accurate Measurement

Clinical Chemistry ◽

10.1373/clinchem.2008.118000 ◽

2009 ◽

Vol 55 (5) ◽

pp. 867-877 ◽

Cited By ~ 109

Author(s):

Duncan J Campbell ◽

Juerg Nussberger ◽

Michael Stowasser ◽

A H Jan Danser ◽

Alberto Morganti ◽

...

Keyword(s):

Plasma Renin Activity ◽

Plasma Renin ◽

Inhibitor Therapy ◽

Renin Activity ◽

Renin Inhibitor ◽

Blood Samples ◽

Hypertensive Patients ◽

Active Renin ◽

Open Conformation ◽

Background Measurement

AbstractBackground: Measurement of plasma renin is important for the clinical assessment of hypertensive patients. The most common methods for measuring plasma renin are the plasma renin activity (PRA) assay and the renin immunoassay. The clinical application of renin inhibitor therapy has thrown into focus the differences in information provided by activity assays and immunoassays for renin and prorenin measurement and has drawn attention to the need for precautions to ensure their accurate measurement.Content: Renin activity assays and immunoassays provide related but different information. Whereas activity assays measure only active renin, immunoassays measure both active and inhibited renin. Particular care must be taken in the collection and processing of blood samples and in the performance of these assays to avoid errors in renin measurement. Both activity assays and immunoassays are susceptible to renin overestimation due to prorenin activation. In addition, activity assays performed with peptidase inhibitors may overestimate the degree of inhibition of PRA by renin inhibitor therapy. Moreover, immunoassays may overestimate the reactive increase in plasma renin concentration in response to renin inhibitor therapy, owing to the inhibitor promoting conversion of prorenin to an open conformation that is recognized by renin immunoassays.Conclusions: The successful application of renin assays to patient care requires that the clinician and the clinical chemist understand the information provided by these assays and of the precautions necessary to ensure their accuracy.

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