Fig. 3.

The pathophysiology of heart failure. Unloading of high-pressure baroreceptors (black circles) in the left ventricle, carotid sinus, and aortic arch generates afferent signals (dashed black lines) that stimulate cardioregulatory centers in the brain, resulting in the activation of efferent pathways in the sympathetic nervous system (dashed grey lines). The sympathetic nervous system appears to be the primary integrator of the neurohumoral vasoconstrictor response to arterial underfilling. Activation of renal sympathetic nerves stimulates the release of renin, thus activating the RAAS. Concomitantly, sympathetic stimulation of the supraoptic and paraventricular nuclei in the hypothalamus results in the nonosmotic release of AVP. Sympathetic activation also causes peripheral and renal vasoconstriction, as does angiotensin II. Angiotensin II constricts blood vessels and stimulates the release of aldosterone from the adrenal gland, and it also increases tubular sodium reabsorption and causes remodeling of cardiac myocytes. Aldosterone may also have direct cardiac effects on fibrosis, in addition to increasing the reabsorption of sodium and the secretion of potassium and hydrogen ions in the collecting duct. The solid black lines designate circulating hormones. Used with permission of Schrier and Abraham [21].