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Cardiovascular Disease 741

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Figure 36-3. The response of a dog to thoracic vena cava constriction and the development of moderate to severe CHF. The first arrow indi-
cates when vena cava constriction was applied. Note the persistent elevation in plasma renin activity (PRA) and plasma aldosterone (PA) con-
centration with a subsequent decrease in urinary sodium excretion and increase in body weight. The second arrow denotes when vena cava
constriction was released. Note the rapid decrease in PRA and PA concentration with marked excretion of excess sodium in the urine and
decrease in body weight. (Adapted from Watkins L, et al. Journal of Clinical Investigation 1976; 57: 1606-1617.)

ticularly those associated with cardiovascular homeostasis ease but no heart failure) or mildly symptomatic left ventricu-
(MacFadyen, 1993; Straeter-Knowlen et al, 1995). ACE activ- lar dysfunction to symptomatic heart failure, neuroendocrine
ity, renin substrate and renin-like enzymatic activity have been mechanisms are progressively activated (Francis et al, 1990).
found in a number of sites including vascular, cardiac, renal, The point at which significant neuroendocrine activation
brain and adrenal tissues.Tissue renin-angiotensin activity may occurs in dogs and cats with spontaneous heart disease and fail-
contribute to the pathophysiology of heart failure, but this is a ure has not been well documented.
topic of considerable debate (Hall and Brands, 1992). Further
studies are needed to elucidate the role of extrarenal renin in the CARDIORENAL INTERACTIONS
development and progression of heart failure. The volume expansion induced by activation of the RAA
AVP is secreted by the posterior lobe of the pituitary gland system is helpful to a point, after which deleterious clinical
in response to nonosmotic stimuli. (See Sympathetic Nervous signs of pulmonary and peripheral edema begin to develop.
System above.) AVP is a potent vasoconstrictor and increases ANP, primarily of atrial origin, counteracts these effects. An
thirst and permeability of cortical and medullary collecting increase in transmural pressure (atrial distention or stretch)
tubules, which allows reabsorption of free water. AVP secretion causes release of ANP, which triggers natriuresis and vasodi-
does not play a major role in the pathogenesis of edema. How- latation. ANP acts directly on the kidneys to: 1) cause diuresis
ever, inappropriate AVP secretion probably plays a role in the through increased sodium and chloride excretion, 2) promote
pathogenesis of the hyponatremia associated with CHF. vasodilatation and 3) suppress aldosterone secretion and plasma
Elevated levels of renin, angiotensin, aldosterone and AVP renin activity. The last effect is presumably a result of the
occur in experimental models of CHF in dogs (Watkins et al, increase in sodium and chloride delivery to the distal tubules
1976; Riegger and Liebau, 1982; Riegger et al, 1988; Maher et and macula densa. Studies have demonstrated a significant
al, 1989; Villarreal et al, 1990; Himura et al, 1994). Plasma natriuretic and diuretic response using physiologic levels of
renin activity and aldosterone concentrations are also increased ANP in normal dogs and dogs with experimental heart failure
in dogs with spontaneous heart disease and failure (Knowlen et (Riegger and Liebau, 1982; Scriven and Burnett, 1985;
al, 1983; Buoro et al, 1992; Pederson et al, 1995). As disease in Zimmerman et al, 1987). The renin-inhibiting effects of ANP
human patients progresses from early asymptomatic (heart dis- may be dependent on the degree of activation of the RAA sys-