Plasma renin concentration

Figure 10. Anti-hypertensive effect of ICI 66082 (300 mg daily) in hypertensive patients, divided according to their plasma renin concentration determined recumbent in the morning (from. Meekers, A. Missotten, R. Fagard, D. Demuynck, C. Harvengt, P. Pas, L. Billiet, and A. Amery in Archives Internationales de Pharma-codynamie et de Therapie)...

Table 1. Impact of RAS Inhibition on Plasma Renin Activity and Plasma Renin Concentration After 8 Weeks of...

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. 

Adrenoceptors are also located on the surface membranes of juxtaglomerular cells, and /3-blockers inhibit the release of renin. However, there is a weak association between plasma renin concentrations and antihypertensive efficacy of /S-blocker therapy. Some patients with low plasma renin concentrations do respond to /3-blockers. Therefore, additional mechanisms also must account for the antihypertensive effect of /3-blockers. However, the ability of /3-blockers to reduce plasma renin and thus angiotensin II concentrations may play a major role in their ability to reduce cardiovascular risk. 

Disease Plasma Renin Concentration Plasma Aldosterone Concentration Blood Pressure... 

There is also clear evidence that the sequel of lead inducing a chronic nephropathy with hypertension can occur. At times, this hypertension may be sufficiently severe to be malignant and may precipitate an early demise [22]. In more chronic cases, the hypertension may be of moderate degree and not be sufficient to cause progressive deterioration of renal function [43]. However, when confronted with a patient with hypertension and mild renal damage, it can be difficult to determine which came first and particularly difficult to determine whether lead was a contributor to the renal damage that caused the hypertension. In such cases, the hypertensive mechanism would be the same as those associated with other varieties of chronic renal disease. By contrast, many patients with chronic lead nephropathy have demonstrated suppressed plasma renin concentrations indicative of a hyporeninemic hypoaldosteronism [44]. 

In normal human subjects, ANP infusion for one hour causes increased absolute and fractional sodium excretion, urine flow, GFR, and water clearance (53—55). As shown in many in vitro and in vivo animal studies, ANP achieves this by direct effect on the sodium reabsorption in the inner medullary collecting duct, ie, by reducing vasopressin-dependent free-water and sodium reabsorption leading to diuresis and by indirect effect through increased hemodynamic force upon the kidney. ANP inhibits the release of renin and aldosterone resulting in the decreased plasma renin activity and aldosterone concentration (56,57). 

Plasma renin activity is elevated after treatment with vasodilators. The hyperreninemia appears to be due in part to enhanced sympathetic nervous activity. Elevated renin levels lead to an increase in the concentration of circulating angiotensin, a potent vasoconstrictor (see Chapter 18) and thus an increase in peripheral vascular resistance. 

Unlike isoflurane, desflurane may stimulate the sympathetic nervous system at concentrations above 1 MAC. Sudden and unexpected increases in arterial blood pressure and heart rate have been reported in some patients, accompanied by increases in plasma catecholamine and vasopressin concentrations and increased plasma renin activity. These pressor effects may increase morbidity or mortality in susceptible patients. The mechanism of sympathetic activation is unclear but does not appear to be baroreceptor-mediated. Clonidine, esmolol, fentanyl and propofol partially block the response but lignocaine (lignocaine) is ineffective. 

Aliskiren is the most advanced of these and the first to be approved for the treatment of hypertension. In healthy subjects, aliskiren produces a dose-dependent reduction in plasma renin activity and Ang I and II and aldosterone concentrations. In patients with hypertension, many of whom have elevated plasma renin levels, aliskiren suppresses plasma renin activity and causes dose-related reductions in blood pressure similar to those produced by ACE inhibitors (Figure 17-3). The safety and tolerability of aliskiren appear to be comparable to angiotensin antagonists and placebo. 

Clonidine reduces plasma renin activity and urinary aldosterone and catecholamine concentrations (291). 

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.)... 

This occurs in hypopituitarism. In theory the best treatment is corticotropin, but the disadvantages of frequent injection are such that hydrocortisone is preferred. Usually less hydrocortisone is needed than in primary insufficiency. Special sodium-retaining hormone is seldom required, for the pituitary has little control over aldosterone production which responds principally to plasma potassium concentration and to the renin-angiotensin system. Thyroxine and sex hormones are given when appropriate. The general conduct of therapy does not differ significantly from that in primary adrenal insufficiency. 

Wade, C. E., and Claybaugh, J. K. (1980). Plasma renin activity, vasopressin concentration, and urinary excretory responses to exercLsc in men. /. Appl. Physic . 49, 930-936. 

In a dose-finding study with bosentan (100,500,1000, and 2000 mg/day) in 293 hjrpertensive patients (5) there were statistically significant falls in diastolic blood pressure with the 500 and 2000 mg/day doses. The effects were similar to that of enalapril 20 mg/day. The lowering of blood pressure was not associated with any changes in heart rate, plasma noradrenaline concentrations, plasma renin activity, or angiotensin II concentrations. 

However, in 85 patients enoxaparin therapy was associated with an increase in mean potassium concentration from 4.26 mmol/1 at baseline to 4.43 mmol/1 on the third day potassium concentrations exceeded 5.0 mmol/1 in 9% (15). There was no life-threatening or sjmptomatic hjrperkalemia. Neither plasma renin activity nor aldosterone concentrations changed significantly and there was no correlation between the increase in potassium concentrations and the presence of diabetes mellitus or treatment with angiotensin converting enzjmes inhibitors, angiotensin receptor blockers, beta-blockers, or potassium-wasting diuretics. 

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