Plasma renin measurement

Latta, J. Improved measurement of plasma renin activity... 

FIGURE 6.4 Kinetic analysis of urea ( ) and inulin H (A) plasma concentrations (upper panel) and renal excretion rates (middle panel) before, during, and after dialysis of a dog with intact kidneys. Inulin was not dia-lyzable but urea concentrations entering and leaving the dialyzer are both shown. The bottom panel shows CLg estimates for urea (—) and inulin (—), and measured plasma renin activity ( ). (Reproduced with permission from Bowsher DJ, Krejcie TC, Avram Mf, Chow MJ, del Greco F, Atkinson AJ Jr. J Lab Clin Med 1985 105 489-97.)... 

Another simple and convenient stimulation test consists of sodium restriction and upright posture. A low-salt diet containing less than 20mmol/da7 of sodium is administered for 3 to 5 daysj urine is collected for creatinine and sodium measurements until equilibrium with the new diet is established. At that point, a plasma renin activity is obtained after 2 hours of standing. A normal response is a twofold to threefold increase in plasma renin output. 

The determination of plasma renin responsiveness, however, is not sufficient to diagnose primary aldosteronism because suppressed PRA also occurs in about 25% of patients with essential hypertension. Primary aldosteronism can be differentiated from other hypermineralocorticoid states on the basis of inappropriate secretion of aldosterone. The demonstration of an elevated concentration of aldosterone in blood or urine in a patient with an unequivocally suppressed PRA concentration (a plasma aldosterone/ plasma PRA ratio >50) is presumptive evidence of primary aldosteronism. Because hypokalemia has a suppressive effect on aldosterone secretion, the potassium deficit should be replaced before aldosterone measurements are done. To establish aldosterone autonomy, the clinician may attempt to suppress aldosterone production with rapid volume expansion (see Box 51-10), with a potent mineralocorticoid (see Box 51-11), or as mentioned with captopril. Failure... 

Used as a screening test, an elevated plasma renin activity after furosemide stimulation or when correlated with urinary sodium excretion can suggest renal artery stenosis as the cause of the hypertension (Figure 51-18). If there is arteriographic evidence for renal artery stenosis, measurement of plasma renin in specimens obtained from selective... 

To obtain the maximum rate of renin activity, saturating amounts of the renin substrate, angiotensinogen, should be present in the reaction system. In most procedures, however, the only substrate provided is that present in the test plasma, and its concentration can be quite variable. According to some investigators, PRA is best estimated when the plasma specimen is incubated with an excess of exogenous renin substrate prepared from nephrectomized human subjects, oxen, or sheep. This type of assay is usually known as a plasma renin concentration assay rather than PRA assay. Unfortunately the measured renin depends on the source and concentration of the renin substrate. Synthetic peptides that resemble the M-terminal portion of angiotensinogen have also been used as renin substrates, but these substances can be hydrolyzed by nonspecific plasma proteases. 

Vaughan ED, Buhler FR, Laragh JH. Renovascular hypertension Renin measurements to indicate hypersecretion and contralateral suppression, estimate renal plasma flow, and score for surgical curability. Am J Med 1973 55 402-14. 

Impaired sodium efflux was measured in leukocytes from patients with essential hypertension. Incubation of normal leukocytes with plasma from hypertensive patients caused impaired sodium transport. 6 Furthermore, partially purified fractions from plasma, as well as urine, inhibit sodium efflux from peripheral blood leukocytesThe severity of the defect in leukocyte cation transport is inversely related to the plasma renin activity and is greatest in patients with essential hypertension in whom the renin response to sodium restriction was atypical. Although these studies support the hypothesis that NH is a digitalis-like substance which inhibits Na, K -ATPase in numerous tissues including the kidney, it remains to be determined whether the natriuretic effect of NH is due exclusively to inhibition of renal Na, K -ATPase. 

It is important to realize how difficult it is to define the in vivo inhibition of ACE. The enzyme may be explored for its N-terminal active sites by measurement of a constant and maximally increased level of N-acetyl SDKP in plasma and urine (211), but the residual activity of the C-ter-minal sites is probably not being measured. The methods for in vitro measurement of plasma ACE, except perhaps that described by Nuss-berger et al. (256), do not appropriately quantify global ACE inhibition. Moreover, the consequences of enzyme blockade are modified by secondary activation of the RAS (233). Residual amounts of angiotensin II secondary to a reactive rise in renin and angiotensin I may explain why the administration of an angiotensin II antagonist still has an additive effect on blood pressure and possibly on the heart, the vessels, and the kidney when added to certain doses of ACE inhibitors (228, 229, 257). 

The activities of renin in plasma and serum are measured in the diagnosis of hypertension. The natural substrate for renin is angiotensin. Several synthetic peptides have been used in renin assays. Recently, Nakamura-lmajo et al. (1992) used N-(2-pyridyl)glycine (pg) as a fluorescent tag on a nonapeptide. 

Concentrations of adrenal mineralocorticoids (e.g., aldosterone and DOC) and factors of the renin-angiotensin system (e.g., renin) are routinely measured in body fluids by various immunoassay and instrument-based methods. Aldosterone, like cortisol, is secreted episodically, with the highest circulating concentrations at about the time of awakening and the lowest concentrations shortly after sleep onset aldosterone concentrations, however, are only modestly stimulated by ACTH secretion.In healthy subjects, a low-sodium diet, maintaining an upright posture, and use of diuretics ail increase plasma aldosterone concentrations,... 

Because inhibitory effects on angiotensin-converting enzyme (ACE) activity, a key enzyme in the renin-angiotensin system, are reported for many hypotensive drugs and functional foods (37,38), the effects of CLA isomers on ACE activity were measured (Fig. 9.6). However, 10r,12c-CLA did not have an inhibitory effect on ACE, because no significant differences were found among the three groups in ACE activity in plasma. 

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