High-output heart failure in the dog: systemic and intrarenal role of angiotensin II

Abstract

Dogs with experimental high-output heart failure (HOF) exhibit marked retention of salt and water secondary to hypersecretion of both renin and aldosterone. The present study was undertaken to evaluate the systemic and intrarenal arteriolar action of angiotensin II (AII) in dogs with HOF and to provide additional information about the role of AII in low-output states. The intravenous infusion of a specific AII antagonist, [Sar1, Ala8]AII (6 mug/kg min-1), into conscious dogs with HOF decreased the mean arterial pressure (AP) from 101 +/- 7 to 83 +/- 7 mmHg (P less than 0.01) after 45 min of infusion. Intrarenal arterial infusion of the AII antagonist (0.2 and 2.0 mug/kg min-1) into anesthetized dogs with HOF also decreased AP and produced a marked increase in renal blood flow (RBF) with no changes in either creatinine clearance or sodium excretion. Similar results were obtained during the intrarenal infusion of the antagonist into sodium-depleted dogs and dogs with thoracic vena caval constriction, but not in normal dogs. The data demonstrate an important role for AII in the regulation of AP and RBF in high- and low-output states.

The role of angiotensin in the control of blood pressure during sodium depletion.

“…The most likely explanation for the blunted reflex is an interference with the central action of All, since an infusion of All into the vertebral artery leads to tachycardia even in the presence of peripheral All blockade. * 8 Since All facilitates the release of norepinephrine from sympathetic nerve endings, 40 an interruption of this effect could also be responsible for the blunted reflex response to the fall in pressure. There is further evidence of a facilitative action of All on the sympathetic nervous system contributing to the maintenance of blood pressure.…”

“…19 " 21 Since the angiotensin antagonists themselves possess properties other than those due to antagonism of the polypeptide, studies have been undertaken in which the response to two different types of antagonists, a converting enzyme inhibitor (CEI) and the competitive antagonist Sar'-Ala 8 angiotensin II (SAR), was measured as renin levels were varied over a wide range in dogs by sodium depletion.…”

Angiotensin antagonists with increased specificity for the renal vasculature.

“…Acute, partial thoracic inferior vena caval occlusion was induced in an additional 16 dogs. P113 induced progressive, doserelated hypotension and a limited increase in renal blood flow in this model.…”

Converting enzyme inhibition and the kidney.

“…18 The important conceptual role played by ablation in defining the action of a hormone in an effector system was pointed out by Haber. 4 In the special case of the interaction of the renin-angiotensin system and the kidney, the kidney is both the source of the hormone and the responding organ.…”

“…suggested that angiotensin, in addition to its systemic effect on blood pressure (BP) and on sodium homeostasis through control of aldosterone secretion, may have a direct action on the renal blood supply. 18 The important conceptual role played by ablation in defining the action of a hormone in an effector system was pointed out by Haber. 4 In the special case of the interaction of the renin-angiotensin system and the kidney, the kidney is both the source of the hormone and the responding organ.…”