Release of renin

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). 

Renin is released by the juxta-glomerular cells when kidney perfusion is impaired. Reduction of the blood volume markedly stimulates release of this enzyme into the blood. The diuretic drug furosemide also markedly stimulates the release of renin. 

Since the discovery of renin over 100 years ago, the RAAS has been extensively studied as a prime target or site of action for many effective antihypertensives.15 Renin is produced and stored in the juxtaglomerular cells of the kidney, and its release is stimulated by impaired renal perfusion, salt depletion, and pr adrenergic stimulation. The release of renin is the rate-limiting... 

A decrease in blood volume or blood pressure may result in a decrease in the blood flow to the kidney. The kidney monitors renal blood flow by way of stretch receptors in the vessel walls. A decrease in renal blood flow stimulates the release of renin. The subsequent secretion of aldosterone causes retention of sodium and water and, therefore, an increase in blood volume and blood pressure back to normal. An increase in renal blood flow tends to cause the opposite effect. 

Describe factors that regulate the release of renin... 

Formation of angiotensin II requires the release of renin from the granular cells. Therefore, the factors affecting renin release must be considered ... 

Atrial natriuretic peptide is released from myocardial cells in the atria of the heart in response to an increase in atrial filling, or an increase in plasma volume. This hormone inhibits the release of renin. With less angiotensin Il-induced vasoconstriction of the afferent arteriole, RBF, GFR, and urine output increase. The increased loss of water and solutes decreases blood volume toward normal. 

Therefore, inhibition of ANP release leads to vasoconstriction and increased MAP. Furthermore, less ANP promotes the release of renin and secretion of aldosterone, which further enhance sodium reabsorption. 

In addition, there is now good evidence indicating that methyldopa effectively suppresses the release of renin by the kidney(23,24). This effect may contribute to the antihypertensive efficacy of the drug in some hypertensive states in which the renin-angiotensin system plays a pathophysiologic role. Thus, it may be concluded that a) methyldopa lowers the blood pressure... 

So, drugs that block jSj-receptors lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen. They are routinely prescribed in patients with ischemic heart disease. In addition, j3-blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood... 

Propranolol lowers blood pressure in the majority of patients with essential hypertension. These effects can be caused by a number of possible mechanisms, including lowering cardiac output, inhibiting the release of renin, lowering sympathetic release from the central nervous system, inhibiting the release of norepinephrine from sympathetic postganglionic nerves, and others. 

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... 

Angiotensin II, the primary end product of the renin-angiotensin system, acts on the juxtaglomerular cells to inhibit the release of renin this process is therefore a negative feedback mechanism. The half-life of renin in the circulation is 10 to 30 minutes, with inactivation occurring primarily in the liver. Small amounts of renin are eliminated by the kidneys. Pure human renin... 

They do not have significant effects on the release of renin or cause long-term changes in lipid or glucose metabolism. 

L A. By blocking renal prostaglandin synthesis, COX-2 inhibitors, such as rofecoxib, decrease the blood flow to the juxtaglomerular apparatus, thus stimulating the release of renin and subsequent Na" retention and blood pressure elevation. Rofecoxib is neither metabolized nor induced by CYP2C9. It decreases rather than increases renal blood flow and does not increase the excretion of hydrochlorothiazide. Item D is incorrect because rofecoxib has very little effect on COX-1 and prostaglandins are not a major controlling factor of peripheral vascular tone. Rofecoxib does not decrease basal metabolic rate. 

The release of renin is altered by a wide variety of pharmacologic agents. Renin release is stimulated by vasodilators (hydralazine, minoxidil, nitroprusside), 13-adrenoceptor agonists, cx-adrenoceptor antagonists, phosphodiesterase inhibitors (eg, theophylline, milrinone, rolipram), and most diuretics and anesthetics. This stimulation can be accounted for by the control mechanisms just described. Drugs that inhibit renin release are discussed below. 

While the angiotensins promote release of aldosterone, the atrial natriuretic hormoner aa cc inhibits release. This group of 21- to 33-residue polypeptides, secreted by cells of the atria (auricles) of the heart, also inhibits release of renin and promotes secretion of both Na+ and water. Thus, they antagonize the action of aldosterone, which promotes Na+ retention. However, there is uncertainty as to the significance of these peptides. The following metabolite of y-tocopherol (Fig. 15-24) has been isolated from urine and is proposed as a new endogenous natriuretic factor.dd... 

Fluid retention A fall in cardiac output decreases blood flow to the kidney, prompting the release of renin, with a resulting increase in the synthesis of angiotensin II and aldosterone (see p. 181). This results in increased peripheral resistance and retention of sodium and water. Blood volume increases, and more blood is returned to the heart. If the heart is unable to pump this extra volume, venous pressure increases and peripheral edema and pulmonary edema occur (Figure 16.4). These compensatory responses increase the work of the heart and, therefore, can contribute to the further decline in cardiac function. 

The (3-blockers reduce blood pressure primarily by decreasing cardiac output (Figure 19.7). They may also decrease sympathetic outflow from the CNS and inhibit the release of renin from the kidneys, thus decreasing the formation of angiotensin II and secretion of aldosterone. The prototype (3-blocker is propranolol, which acts at both (3i and (32 receptors. Newer agents, such as atenolol and meto-prolol, are selective for [3-i receptors. These agents are commonly used in disease states such as asthma, in which propanolol is contraindicated due to its (32-mediated bronchoconstriction. (See p. 73 for a complete discussion of (3-blockers.)... 

Antagonism of ft i-receptors on the juxtaglomerular cells of the kidney that reduce the release of renin. 

Increased activity of the renin-angiotensin system is frequently observed in kidney disease, which may lead to abnormally high release of renin. Several points in the system are amenable to pharmacological inhibition. The first one is renin itself, which splits a specific bond in the angiotensino-gen polypeptide chain (Figure 1.5a). An inhibitor of renin is remikiren (Figure 1.6a). 

Inorganic cobalt is transported in the blood by albumin and transferrin it is taken up by the liver. The serum concentration amounts to 1.9-7.6 mmol/1. An increased value is a sign of liver cell necrosis (e. g. acute hepatitis). Its biological significance is attributed to its position as a central atom in vitamin B12 and its involvement in the release of renin and erythropoietin. 

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