Hepatic Clearance of Renin in Canine Experimental Models for Low- and High-Output Heart Failure

Abstract

Hepatic blood flow, hepatic extraction of renin, and hepatic clearance of renin were compared in normal conscious dogs, in dogs with constriction of the thoracic inferior vena cava (as a model of low-output heart failure), and in dogs with an aortic-caval fistula (high-output heart failure). Both "failure" preparations showed marked sodium retention. Renin was measured by methods described previously and expressed as nanograms of angiotensin produced during incubation per milliliter of plasma. Hepatic plasma flow was determined by the sodium sulfobromophthalein method. The dogs with low-output heart failure had a marked reduction in hepatic plasma flow, while those with high-output failure showed no significant change in this flow. Plasma renin was significantly elevated in both models of heart failure. Dogs with low-output failure had an increase (P<.05) in hepatic renin extraction from a normal value of 19.8% to 33.4%, while those with high-output failure showed a decrease in hepatic renin extraction to 11.9% (P<.01). The hepatic clearance of renin in low-output failure (104 ml/ min) was the same as the average normal value of 104 ml/min, while clearance of renin by the liver in high-output failure was reduced to 51 ml/min (P<.001). The data provide evidence that the decreased metabolism of renin contributes substantially to the increased plasma level of renin in experimental high-output heart failure. ADDITIONAL KEY WORDS hepatic extraction of renin sodium retention thoracic inferior vena caval constriction aortic-caval fistula plasma renin hepatic blood flow chronic venous congestion• In congestive heart failure, in decompensated cirrhosis of the liver, and in their experimental counterparts, elevated plasma renin levels (1-7) have been causally related in increased aldosterone secretion. The exact mechanisms which lead to an elevated plasma renin have not been clearly defined. Haecox, et al. (8) have demonstrated in anesthetized dogs that significant extraction or inactivation of renin is brought about by the liver. In view of the hepatic congestion associated with right heart failure, it was decided to investigate the role of the hepatic metabolism of renin in the elevated plasma renin levels found in experimental heart failure. Hepatic blood flow, hepatic renin extraction, and the hepatic clearance of renin were measured in normal conscious dogs and in conscious dogs with either constriction of the thoracic inferior vena cava or an aortic-caval fistula.Constriction of the thoracic inferior vena cava was used to produce a model of lowoutput heart failure. Although such animals are not in true congestive heart failure, it has been demonstrated that the salt and

Mechanisms regulating the renal excretion of sodium during pregnancy

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“…These considerations raise the question of the possible role of estrogens in increasing aldosterone secretion by a nonrenin mechanism. There is also the possibility of a decrease in renin metabolism by the liver (19) as a contributory mechanism to the high plasma renin activity, but no data are available on this point. There remains the question of whether the high plasma level of estrogens achieved during exogenous hormone administration is present during pregnancy.…”

Renal-Portal Shunt to Restore Normal Reninism and Blood Pressure in Experimental Renovascular Hypertension in Dogs

“…Thus it has been suggested that the liver is the major site of renin metabolism. [1][2][3][4][5][6] This observation is supported by the finding that reduced hepatic blood flow induces a marked increase in arterial renin by an elective decrease in hepatic extraction of renin. 1,2,7 It has also been reported that following hepatic damage due to carbon tetrachloride intoxication in dogs, the difference between PRA values in hepatic and portal veins is no longer appreciable.'…”

Plasma Renin Activity and the Effects of Deoxycorticosterone Acetate in Dogs with Chronic Left Ventricular Overload

“…Blood was drawn from the jugular vein (10 ml) and collected in ethylenediamine tetraacetate (EDTA) for the determination of plasma renin activity by the technique described by Schneider et al (3). A 3-hour incubation was done and the amount of angiotensin II formed assayed in the vagotomized, ansolysin-treated rat.…”