Pulmonary hypertension, right ventricular failure, and kidney: different from left ventricular failure?

Abstract

In this article, the pathophysiology of left ventricular failure is reviewed. By contrast, the paucity of information about pulmonary arterial hypertension and right ventricular failure is acknowledged. The potential mechanisms whereby renal sodium and water retention in right ventricular failure secondary to pulmonary arterial hypertension can occur, despite normal left ventricular function, are discussed. With right ventricular failure as the primary cause of death in patients with pulmonary hypertension, more information about the mechanisms of renal sodium and water retention in these patients is direly needed. Specifically, studies to examine the activation of the neurohumoral axis at various stages of pulmonary arterial hypertension and right ventricular failure, including inhibition of mineralocorticoid and V2 vasopressin receptors, are indicated.

Figure 1.

Unloading of high-pressure baroceptors (blue circles) in the left ventricle, carotid sinus, and aortic arch generates afferent signals (black) that stimulate cardioregulatory centers in the brain, resulting in the activation of efferent pathways in the sympathetic nervous system (green). The sympathetic nervous system seems to be the primary integrator of the neurohumoral vasoconstrictor response to arterial underfilling. Activation of renal sympathetic nerves stimulates the release of renin and angiotensin II, thereby activating the renin-angiotensin-aldosterone system (RAAS). Concomitantly, sympathetic stimulation of the supraoptic and paraventricular nuclei in the hypothalamus results in the nonosmotic release of arginine vasopressin (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 blue lines designate circulating hormones. Reprinted from reference 2 (Schrier RW, Abraham WT: Hormones and hemodynamics in heart failure. N Engl J Med 341: 577–585, 1999), with permission. Copyright © 1999 Massachusetts Medical Society. All rights reserved.

Figure 2.

Feedback mechanisms for normalizing neurohormones and cardiac index with myocardial injury. The dashed lines indicate the compensatory responses that could return cardiac index and the RAAS to within normal range.