CHANGES IN THE RENIN-ANGIOTONIN SYSTEM IN HEMORRHAGIC SHOCK

Abstract

Modifications of the procedure of Wiggers and his associates for the production of hemorrhagic shock were employed in dogs, anesthetized usually with morphine and barbital. Endogenous angiotonin (hypertensin) and renin-substrate (hypertensinogen) were detd. semi-quantitatively in plasma by bio-assay on the ileum of the guinea pig, on the perfused rabbit''s ear, and on the intact animal. Complication of the assay by endogenous adrenalin was excluded by bilateral adrenalectomy or by inactivation of adrenalin in the samples by formaldehyde. Following varying periods of hypotension significant reductions in renin-substrate were observed in 10 of 15 intact dogs. A period of moderate hypotension (e.g., ca. 50 mm. Hg for 90 min.) followed by a period of drastic hypotension (ca. 30 mm. Hg) was required in most animals. Reduction in renin-substrate was also observed in 3 of 10 adrenalectomized dogs following hypotension. The data suggested that reduction occurred less readily than in intact dogs. A preliminary increase in renin-substrate frequently was observed early in hemorrhage in both intact and adrenalectomized dogs. Six of 7 recently nephrectomized dogs, 3 of which also were adrenalectomized, showed progressive increases in renin-substrate during hypotension. Bled intact dogs consistently showed increases in an angiotonin-like substance which contracted the ileum of the guinea pig, elevated blood pressure in dogs and cats, and caused vasoconstriction in the rabbit''s ear. A secondary fall in this substance occurred subsequent to depletion of renin-substrate. Nephrectomized dogs subjected to hypotension failed to show significant rises in angiotonin-like substance.