Aldosteronism Baroreceptors

There is another system involved in blood pressure regulation the renin-angiotensin-aldosterone system (Fig. 2). The arterial blood pressure in the kidney influences intrarenal baroreceptors which together with the sodium load at the macula densa lead to renin liberation, angiotensin formation and aldosterone secretion, which by influencing the sodium balance changes the blood volume and influences the arterial blood pressure. 

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. 

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... 

Diuretics are the mainstay of heart failure management and are discussed in detail in Chapter 15. They have no direct effect on cardiac contractility their major mechanism of action in heart failure is to reduce venous pressure and ventricular preload. This results in reduction of salt and water retention and edema and its symptoms. The reduction of cardiac size, which leads to improved pump efficiency, is of major importance in systolic failure. Spironolactone and eplerenone, the aldosterone antagonist diuretics (see Chapter 15), have the additional benefit of decreasing morbidity and mortality in patients with severe heart failure who are also receiving ACE inhibitors and other standard therapy. One possible mechanism for this benefit lies in accumulating evidence that aldosterone may also cause myocardial and vascular fibrosis and baroreceptor dysfunction in addition to its renal effects. 

In most cases, elevated blood pressure is associated with an overall increase in resistance to flow of blood through arterioles, while cardiac output is usually normal. Meticulous investigation of autonomic nervous system function, baroreceptor reflexes, the renin-angiotensin-aldosterone system, and the kidney has failed to identify a primary abnormality as the cause of increased peripheral vascular resistance in essential hypertension. 

Pathophysiology In HF patients, the levels of aldosterone are elevated, even in the presence of ACE inhibitors or angiotensin-receptor blockers (34,35). Aldosterone has detrimental effects in HE such as causing potassium and magnesium loss, sodium retention, baroreceptor dysfunction, and myocardial fibrosis it also decreases the neuronal uptake... 

Aldosterone is expected to work in concert with ADH. Thus, if the appropriate baroreceptors (monitors of blood pressure) should detect decreased blood... 

The short-term mechanism for BP control centres on the baroreceptor reflex. The long-term mechanism involves the renin-angiotensin system and body sodium control via aldosterone. 

The compensatory responses to hydralazine use are tachycardia and salt and water retention. These responses are generated by the baroreceptor and renin-angiotensin-aldosterone mechanisms summarized in Figure 6-4. The motor limb of the sympathetic response consists of outflow from the vasomotor center to the heart and vessels, as shown in Figure 11-3. You should be able to reproduce these diagrams from memory. 

Secondary aldosteronism results in high blood levels of aldosterone in the absence of a primary adrenal defect. Secondary aldosteronism develops when one of the stimuli of aldosterone secretion is overactive. Consequently, at least three types of conditions can lead to secondary aldosteronism excess of renin, ACTH, or potassium. The condition encountered most often clinically is that in which renin is overproduced because of increased secretion by the juxtaglomerular apparatus or, more rarely, because of overproduction of precursors or extrarenal secretion (for example, by tumors). Renal secretion is stimulated when (1) arterial blood flow to the kidney is reduced (stimulation of baroreceptors), either as a result of the reduction in effective blood volume or renal artery obstruction or (2) osmoreceptors are stimulated as a result of hyponatremia. The arterial blood volume can be reduced by factors that decrease the blood volume (reduced water, sodium, or both), passage of fluid from the blood vessels to the extracellular compartment, and pregnancy (see Table 9-1). 

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