Angiotensin aldosterone release

Stimulates Renin-angiotensin-aldosterone release ADH secretion Sympathetic response —> vasoconstriction Inhibits ANP secretion Stimulates ANP secretion Arteriole vasodilation Inhibits ADH secretion Renin-angiotensin-aldosterone secretion... 

Adrenal Inhibition of angiotensin II stimulated aldosterone release... 

Hyperkalemia results from reduced angiotensin II-stimulated aldosterone release. The risk of hyperkalemia with ACE... 

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. 

The zona glomerulosa is responsible for the production of the mineralocorticoids aldosterone, deoxycorticosterone, and 18-hydroxy-deoxycorticosterone. Aldosterone promotes renal sodium retention and excretion of potassium. Its synthesis and release are regulated by renin in response to decreased vascular volume and renal perfusion. Adrenal aldosterone production is regulated by the renin-angiotensin-aldosterone system. 

Once vasodilatation was considered to be a good strategy, as it improves HF symptoms. However later studies showed that the disease itself was not influenced. The accent of HF treatment has moved to progression prevention with rigorous suppression of the renin angiotensin aldosterone system. Therapy with /3-blockers was also proven to be effective for the reduction of mortality. These treatments should be started early and the evaluation of their effectiveness in individual patients is difficult. As brain natriuretic peptide (BNP) is produced by the heart and more BNP is released in heart failure, the measurement of BNP in the blood has become popular as surrogate marker for the severity of heart failure and for the response of treatment for heart failure. 

Captopril, as well as other ACE inhibitors, is indicated in the treatment of hypertension, congestive heart failure, left ventricular dysfunction after a myocardial infarction, and diabetic nephropathy. In the treatment of essential hypertension, captopril is considered first-choice therapy, either alone or in combination with a thiazide diuretic. Decreases in blood pressure are primarily attributed to decreased total peripheral resistance or afterload. An advantage of combining captopril therapy with a conventional thiazide diuretic is that the thiazide-induced hypokalemia is minimized in the presence of ACE inhibition, since there is a marked decrease in angiotensin Il-induced aldosterone release. 

Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11-1) arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of vasoactive substances from vascular endothelium may also be involved in the regulation of vascular resistance. For example, endothelin-1 (see Chapter 17) constricts and nitric oxide (see Chapter 19) dilates blood vessels. 

Neurohumoral (extrinsic) compensation involves two major mechanisms (previously presented in Figure 6-7)—the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal response—plus several others. Some of the pathologic as well as beneficial features of these compensatory responses are illustrated in Figure 13-2. The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure, in patients with heart failure. As a result, baroreceptor sensory input to the vasomotor center is reduced even at normal pressures sympathetic outflow is increased, and parasympathetic outflow is decreased. Increased sympathetic outflow causes tachycardia, increased cardiac contractility, and increased vascular tone. Vascular tone is further increased by angiotensin II and endothelin, a potent vasoconstrictor released by vascular endothelial cells. The result is a vicious cycle that is characteristic of heart failure (Figure 13-3). Vasoconstriction increases afterload, which further reduces ejection fraction and cardiac output. Neurohumoral antagonists and vasodilators... 

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... 

In addition to the angiotensin II effects, aldosterone secretion is regulated by increased plasma potassium levels.75,83 Presumably, elevated plasma potassium serves as a stimulus to increase aldosterone release, thus causing increased potassium excretion and a return to normal plasma levels. Finally, there is evidence that ACTH may also play a role in aldosterone release. Although ACTH is primarily involved in controlling glucocorticoid secretion, this hormone may also stimulate mineralocorticoid release to some extent.75... 

FIGURE 10.5 Results of a study on rat zona glomcrulosii cells. The effect of angiotensin II w as measured as the amount of aldosterone released into the medium by the cells. (Redrawn with permission from Braley ei a ., 1989.)... 

The interaction of cyclosporine with the plasma and tissue renin-angiotensin-aldosterone systems (RAS) has been extensively studied [21, 22]. Sodium depletion, a condition that stimulates renin release, enhances acute CSA nephrotoxicity [23, 24]. In rats, CSA treatment enhanced plasma renin activity (PRA) [21, 25, 26], increased renal renin content [21], promoted juxtaglomerular hypertrophy and hyperplasia [27,... 

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