Renin-angiotensin-aldosterone system vasodilators

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. 

Nesiritide is manufactured using recombinant techniques and is identical to the endogenous B-type natriuretic peptide secreted by the ventricular myocardium in response to volume overload. Consequently, nesiritide mimics the vasodilatory and natriuretic actions of the endogenous peptide, resulting in venous and arterial vasodilation increases in cardiac output natriuresis and diuresis and decreased cardiac filling pressures, sympathetic nervous system activity, and renin-angiotensin-aldosterone system activity. 

About 50% of patients with cirrhosis develop ascites within 10 years of diagnosis and 50% of these will die within 2 years. The process by which ascites forms in cirrhosis is not fully understood but appears to involve the accumulation of vasodilator substances, activation of the renin-angiotensin-aldosterone system (causing renal retention of sodium and water), and the production of antidiuretic hormone (causing hyponatraemia due to dilution, not deficiency, of plasma sodium). 

Increased intrahepatic resistance to portal flow increases pressure on the entire splanchnic bed an enlarged spleen (splenomegaly) is a common finding in cirrhotic patient and can result in thrombocytopenia due to splenic sequestration of the platelets. Portal hypertension mediates systemic and splanchnic arterial vasodilation through production of nitric oxide and other vasodilators in an attempt to counteract the increased pressure gradient. Nitric oxide causes a fall in systemic arterial pressure unfortunately, this activates both the renin-angiotensin-aldosterone and sympathetic nervous systems and... 

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... 

Counterregulation in acute hypotension due to vasodilators (B). Increased sympathetic drive raises heart rate (reflex tachycardia) and cardiac output and thus helps to elevate blood pressure. The patients experience palpitations. Activation of the renin-angiotensin-aldosterone (RAA) system serves to increase blood volume, hence cardiac output. Fluid retention leads to an increase in body weight and, possibly, edemas. 

The renin—angiotensin—aldosterone and sympathetic nervous systems are the main homeostatic effectors of vasoconstriction and sodium retention, paralleled by vaso-pressin/adiuretin activation. They all act synergistically but, at the same time, are balanced by counter-regulatory vasodilator and natriuretic mechanisms, particularly the natriuretic peptides and the NO system, also interplaying with endothelial redox systems, inflammatory cytokines and growth factors (Kaplan, 2002). 

Chapter 12 contains additional discussion of vasodilators. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Sodium nitroprusside and the nitrates also relax veins. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system (Figure 11-4), as well as renin, angiotensin, and aldosterone. Because sympathetic reflexes are intact, vasodilator therapy does not cause orthostatic hypotension or sexual dysfunction. 

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