efferent neural pathways emanating from high-pressure areas inhibited the natriuretic response to volume expansion (18, 19, 20). Moreover, reduction of pressure or stretch at the carotid sinus, similar to that produced by decreased cardiac output or arterial hypotension, has been shown to activate the sympathetic nervous system and promote renal sodium and water retention (21). High-pressure baroreceptors also appear to be important factors in regulating nonosmotic release of AVP and thus renal water excretion (22). One of the best-defined high-pressure receptors that are known to act in an appropriate manner to maintain constancy of the EABV is the renal afferent arteriolar baroreceptor (i.e., juxtaglomerular apparatus). This baroreceptor is an important factor in the control of renal renin secretion and consequently angiotensin II formation and aldosterone synthesis and release (23). The vasoconstrictor and sodium-retaining effects of angiotensin II and sodium-retaining effect of aldosterone then act to restore the fullness of the arterial circulation.
patients with chronic heart failure (38). Taken together, these findings suggest that the normal inhibitory control of sympathetic activation accompanying increased atrial pressures is lost in heart failure patients and somehow may even be converted to a stimulatory signal.
Table 2-1 Body Fluid Distribution
heart failure, whereas systemic arterial vasodilation initiates the afferent limb of sodium and water retention in high-output cardiac failure (Fig. 2-1).
ventricular dysfunction (i.e., before the onset of overt heart failure) (54). Finally, studies employing peroneal nerve microneurography to directly assess sympathetic nerve activity to muscle have confirmed the presence of increased sympathetic activity in heart failure patients (55). Significantly, the degree of activation of the sympathetic nervous system—as assessed by the peripheral venous plasma norepinephrine concentration—has been correlated with poor prognosis in heart failure (56).
this investigation, the observation that losartan restored renal responsiveness to ANP is consistent with a losartan-induced increase in the delivery of sodium to the distal tubular site of ANP action. The role of distal tubular sodium delivery in the renal sodium retention of heart failure is discussed later.
ADHERE registry, inhibiting the secondary hyperaldosteronism in sodium-retaining CHF patients who are diuretic resistant needs to be undertaken. Isotonic removal of sodium in CHF patients with ultrafiltration is another therapeutic approach. Fluid removal in CHF patients with ultrafiltration or diuretics can improve cardiac and renal function in addition to treating pulmonary congestion and edema. The mechanisms are shown in Figure 2-4 (74).
coronary-ligated rats with CHF. The latter group also demonstrated that AQP1 and AQP3 were not upregulated in this CHF model and that increased trafficking of the AQP2 to the apical membrane occurred. Our group further showed that a V2 vasopressin antagonist reversed the upregulation of the AQP2 protein in the renal cortex and medulla of the CHF rats (81). This effect of the nonosmotic release of AVP to cause water retention in cardiac failure recently has been associated with increased transcription of messenger RNA (mRNA) for the AVP preprohormone in the rat hypothalamus (84).
coronary ligation model of heart failure in rats, the infusion of a monoclonal antibody shown to specifically block endogenous ANP in vivo caused a significant rise in right atrial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance (96). Thus, natriuretic peptides appear to attenuate to some degree the arterial and venous vasoconstriction of heart failure.
Downregulation of renal ANP receptors
Secretion of inactive immunoreactive ANP
Enhanced renal neutral endopeptidase activity limiting the delivery of ANP to receptor sites
Hyperaldosteronism causing increased sodium reabsorption in the distal renal tubule
Diminished delivery of sodium to the distal renal tubule site of ANP action