Plasma renin

Patients having high plasma renin activity (PRA) (>8 ng/(mLh)) respond best to an ACE inhibitor or a -adrenoceptor blocker those having low PRA (<1 ng/(mLh)) usually elderly and black, respond best to a calcium channel blocker or a diuretic (184). -Adrenoceptor blockers should not be used in patients who have diabetes, asthma, bradycardia, or peripheral vascular diseases. The thiazide-type diuretics (qv) should be used with caution in patients having diabetes. Likewise, -adrenoceptor blockers should not be combined with verapamil or diltiazem because these dmgs slow the atrioventricular nodal conduction in the heart. Calcium channel blockers are preferred in patients having coronary insufficiency diseases because of the cardioprotective effects of these dmgs. 

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). 

In an attempt to conserve sodium, the kidney secretes renin increased plasma renin activity increases the release of aldosterone, which regulates the absorption of potassium and leads to kafluresis and hypokalemia. Hypokalemia is responsible in part for decreased glucose intolerance (82). Hyponatremia, postural hypotension, and pre-renal azotemia are considered of tittle consequence. Hypemricemia and hypercalcemia are not unusual, but are not considered harmful. However, hypokalemia, progressive decreased glucose tolerance, and increased semm cholesterol [57-88-5] levels are considered... 

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

As previously discussed, increased portal pressure triggers the release of nitric oxide to directly vasodilate the splanchnic arterial bed and decrease portal pressure. Unfortunately, nitric oxide also dilates the systemic arterial system, causing a decrease in blood pressure and a decrease in renal perfusion by lowering the effective intravascular volume. The kidney reacts by activating the renin-angiotensin-aldosterone system, which increases plasma renin activity, aldosterone production, and sodium retention. This increase in intravascular volume furthers the imbalance of intravascular oncotic pressure, allowing even more fluid to escape to the extravascular spaces. 

Robertson, D., Frolich, J., Carr, R., Watson, J., FFollifield, J., Shand, D., and Oates, J., Effects of caffeine on plasma renin activity, catecholamines, and blood pressure, New England Journal of Medicine, 298, 181, 1978. 

Limited data on occupationally exposed men indicate that the effect of lead on blood pressure may be mediated in part through the renin-angiotensin system, as evidenced by lead-related increases in plasma renin and angiotensin I levels (Campbell et al. 1985) and the kallikrein-kinin system, as indicated by a correlation between renin and kallikrein (Boscolo et al. 1981). Evidence from patients with essential hypertension and renal impairment suggests that excessive lead absorption may be involved in the development of both conditions (Batuman et al. 1983). 

Boscolo P, Galli G, Iannaccone A, et al. 1981. Plasma renin activity and urinary kallikrein excretion in lead-exposed workers as related to hypertension and nephropathy. Life Sci 28 175-184. 

More specific laboratory tests are used to diagnose secondary hypertension. These include plasma norepinephrine and urinary metanephrine levels for pheochromocytoma, plasma and urinary aldosterone levels for primary aldosteronism, and plasma renin activity, captopril stimulation test, renal vein renins, and renal artery angiography for renovascular disease. 

I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion. ACE inhibitors also block the degradation of bradykinin and stimulate the synthesis of other vasodilating substances including prostaglandin E2 and prostacyclin. The fact that ACE inhibitors lower BP in patients with normal plasma renin activity suggests that bradykinin and perhaps tissue production of ACE are important in hypertension. 

Aliskiren blocks the renin-angiotensin-aldosterone system at its point of a activation, which results in reduced plasma renin activity and BP. It provides BP reductions comparable to an ACE inhibitor, ARB, or CCB. It also has additive antihypertensive effects when used in combination with thiazides, ACE inhibitors, ARBs, or CCBs. It is approved for monotherapy or in combination with other agents. 

Clonidine, guanabenz, guanfacine, and methyldopa lower BP primarily by stimulating a2-adrenergic receptors in the brain, which reduces sympathetic outflow from the vasomotor center and increases vagal tone. Stimulation of presynaptic oq-receptors peripherally may contribute to the reduction in sympathetic tone. Consequently, there may be decreases in heart rate, cardiac output, total peripheral resistance, plasma renin activity, and baroreceptor reflexes. 

Hypertension is more common and more severe in African Americans than in those of other races. Differences in electrolyte homeostasis, glomerular filtration rate, sodium excretion and transport mechanisms, plasma renin activity, and BP response to plasma volume expansion have been noted. 

Buhler et al (52) observed that patients with high plasma renin values generally responded well to propranolol while those with abnormally low values responded poorly Figure 9. More recent studies have confirmed that the plasma renin value is a useful index to those patients who are more likely to respond to (3-blocking therapy. Figure 10 shows the results from a trial by Amery et al using ICI 66082 (20)... 

Since it has been reported that hypertensive patients with high plasma renin levels suffer a higher incidence of vascular complications, the use of (3-blocking drugs would seem to be particularly beneficial to this class of patient (55). 

Although a high level of plasma renin appears to identify a subject likely to respond to (3-blockers the relationship between the reduction in renin level and fall in blood pressure is still obscure. While some investigators claim good correlations between the reduction in renin and blood pressure others find no such correlation (20). In fact, Stokes et al (34) showed that pindolol was able to maintain the fall in blood pressure produced by chronic administration of propranolol without maintaining the reduction in renin. 

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)...

Specialized cells, called the juxtaglomerular apparatus (JGA), within the renal cortex are able to detect a fall in blood pressure and respond by secreting a proteolytic enzyme called renin (not to be confused with rennin). The substrate for renin, a liver-derived peptide called angiotensinogen, circulates in the plasma. Renin removes two amino acids from the N-terminal to produce angiotensin I, which is itself a substrate for angiotensin-converting enzyme (ACE). ACE removes two more amino acids to produce angiotensin II. 

Similar activities have been found on A-alky-iV-2,2-dimethylvinylimino-phosphate (88MI1). N-Carbonyltriaryliminophosphoranes (42 Scheme 21), which have been employed as diuretics, have been shown to decrease plasma-renine activity (88USP4767749). 

Renin [2] is an aspartate proteinase (see p. 176). It is formed by the kidneys as a precursor (prorenin), which is proteolytically activated into renin and released into the blood. In the blood plasma, renin acts on angiotensinogen, a plasma glycoprotein in... 

Pharmacology The proposed mechanism of action of methyidopa is probably due to the drug s metabolism to alpha-methyl norepinephrine, which lowers arterial pressure by the stimulation of central inhibitory -adrenergic receptors, false neurotransmission or reduction of plasma renin activity. 

Adenosine 2a receptor ADORA2A Agonism Inhibition of platelet aggregation, anti-inflammation and neuroprotective effects, coronary vasodilation, decreased blood pressure, increased plasma renin activity and sleep induction. Antagonism Increased platelet aggregation, hypertension, nervousness (tremor, agitation), arousal, insomnia, cerebral and coronary vasodilation (in microvessels only). 

Compound No. Structure IC50 (M), Human Plasma Renin... 

Reduction in plasma volume secondary to the enhanced excretion of sodium ions and water and the regression of edema, if present. These effects are accompanied by a reduction in cardiac preload. During long-term treatment most of these effects are counteracted by various regulatory mechanisms, such as a persistent rise in plasma renin and aldosterone. 

These potent diuretic agents interact with almost the entire nephron, including Henle s loop (Fig. 7). Their primary effect is probably the inhibition of the active reabsorption of chloride ions, which then leads to the enhanced excretion of sodium ions and water. Plasma volume is reduced as a result of these effects, whereas in the long-term both cardiac preload and afterload will diminish. The metabolic side-effects of the loop diuretics are globally the same as those of the thiazides, with some incidental differences. Plasma renin activity increases by loop diuretic treatment and it can be well imagined that this effect is noxious in the long-term management of heart failure. The loop diuretics provoke a clearly... 

Thiazide diuretics are effective antihypertensive agents in black hypertensive patients and studies suggest that they cause a greater decrease in blood pressure in black patients than in whites. The better hypotensive response in black hypertensive patients is probably due to the fact that, in comparison with whites, more black patients have an expanded intracellular volume and low plasma renin activity. In developing countries, in which the majority of black people live, the cost of therapy is important. Thiazide diuretics are because of their low cost important baseline drugs in the treatment of hypertension. 

Arterial blood pressure (afterload) is also reduced by propranolol. Although the mechanisms responsible for this antihypertensive effect are not completely understood, they are thought to involve (1) a reduction in cardiac output, (2) a decrease in plasma renin activity, (3) an action in the central nervous system, and (4) a resetting of the baroreceptors. Thus, propranolol may exert a part of its benehcial effects in secondary angina by decreasing three of the major determinants of myocardial oxygen demand, that is, heart rate, contractihty, and systolic wall tension. 

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