![]() Finally, angiotensin II may increase the release of arginine vasopressin via a mechanism that does not rely on changes in osmolality, leading to renal free water reabsorption and dilutional hyponatremia seen with severe HF. The abnormal hypertrophy and fibrosis increase the passive stiffness of the ventricles and arterial bed, interfering with ventricular filling and reducing arterial compliance and, along with myocyte slippage and interstitial growth, result in ventricular remodeling. Increased circulating levels of angiotensin II also promote the release of aldosterone from the adrenal zona glomerulosa, resulting in sodium reabsorption and potassium excretion in the distal nephron, along with myocardial fibroblast proliferation and collagen deposition. Angiotensin-converting enzyme (ACE) cleaves two amino acids from angiotensin I to form the biologically active angiotensin II, which binds to vascular angiotensin receptors causing vasoconstriction of the efferent postglomerular arterioles (promoting reabsorption of sodium, urea, and water) and to cardiac angiotensin receptors causing myocyte hypertrophy, apoptosis, and interstitial fibrosis. ![]() Renin cleaves four amino acids from circulating angiotensinogen to form the biologically inactive angiotensin I. The mechanisms for RAAS activation in HF include renal hypoperfusion with decreased filtered sodium reaching the macula densa and decreased stretch of the juxtaglomerular apparatus leading to increased renin release. These functional and structural myocardial changes result in compensatory activation of neurohormonal systems, such as the renin–angiotensin–aldosterone system (RAAS), the adrenergic system, and the hypothalamic–neurohypophyseal system. After the initial compensatory phase, the increase in ventricular volume is associated with further reductions in the ejection fraction (progressive systolic dysfunction) and with abnormalities in the peripheral circulation from activation of various neurohormonal compensatory mechanisms. Eventually, the compensatory force of the normal myocardial contraction decreases as cell loss and hypertrophy continue, leading to increased ventricular volume (“cardiac remodeling”) and significant geometric ventricular alterations (ellipsoid to spherical shape). ![]() The biochemical, electrophysiologic, and contractile changes that ensue lead to alterations in the mechanical properties of the myocardium. ![]() When an excessive workload is imposed on the heart by increased systolic blood pressure (pressure overload, such as in chronic hypertension or aortic stenosis), increased diastolic volume (volume overload, such as in progressive dilated idiopathic cardiomyopathy or chronic aortic or mitral regurgitation), or loss of myocardium (acutely in the setting of myocardial infarction, or chronically in the setting of flow-limiting coronary artery disease), normal myocardial cells hypertrophy in order to increase the contractile force of the unaffected areas. ![]()
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