Plasma-renin activity

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. 

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. 

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). 

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). 

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. 

Three generally accepted mechanisms are involved in the regulation of renin secretion (Fig. 18.2). The first depends on renal afferent arterioles that act as stretch receptors or baroreceptors. Increased intravascular pressure and increased volume in the afferent arteriole inhibits the release of renin. The second mechanism is the result of changes in the amount of filtered sodium that reaches the macula densa of the distal tubule. Plasma renin activity correlates inversely with dietary sodium intake. The third renin secretory control mechanism is neurogenic and involves the dense sympathetic... 

The hypotensive response to captopril is accompanied by a fall in plasma aldosterone and angiotensin II levels and an increase in plasma renin activity. Serum potassium levels are not affected unless potassium supplements or potassium-sparing diuretics are used concomitantly this can result in severe hyperkalemia. 

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. 

The reduction in plasma volume produced by p-blockers contrasts with the increased volume seen with other types of antihypertensives. Tolerance to the antihypertensive actions of p-blockers therefore is less of a problem than with the vasodilating drugs. An additional difference from the vasodilators is that plasma renin activity is reduced, rather than increased, by propranolol (Inderal). Orthostatic hypotension does not occur with p-blockers. 

An important aspect of a-methyldopa s hemodynamic effects is that renal blood flow and glomerular filtration rate are not reduced. As occurs with most sympathetic depressant drugs and vasodilators, long-term therapy with a-methyldopa leads to fluid retention, edema formation, and plasma volume expansion. While data conflict somewhat, it is generally thought that a-methyldopa suppresses plasma renin activity. 

Renal blood flow and glomerular filtration are not decreased, although renal resistance is diminished. Like a-methyldopa, it is a useful agent for hypertension complicated by renal disease. Plasma renin activity is reduced by clonidine, presumably as a result of a centrally mediated decrease in sympathetic stimulation of the juxtaglomerular cells of the kidney. 

Renin-angiotensin-aldosterone system activity. Plasma renin activity and enzyme-... 

Mechanism of Action AnACE inhibitor that suppresses the renin-angiotensin-aldos-terone system and prevents conversion of angiotensin I to angiotensin 11, a potent vasoconstrictor may also inhibit angiotensin II at local vascular and renal sites. Decreases plasma angiotensin II, increases plasma renin activity, and decreases aldosterone secretion. Therapeutic Effect Reduces peripheral arterial resistance, pulmonary capillary wedge pressure improves cardiac output and exercise tolerance. Pharmacokinetics ... 

Mechanism of Action An antihypertensive agent that stimulates central inhibitory alpha-adrenergic receptors, lowers arterial pressure, and reduces plasma renin activity. Therapeutic Effect Reduces BP. 

Mechanism of Action An ACE inhibitor that suppresses the renin-angiotensin-aldosterone system. Decreases plasma angiotensin II, increases plasma renin activity, and decreases aldosterone secretion. Therapeutic Effect Reduces peripheral arterial resistance and BP. 

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