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Plasma reninlike activity significantly increased in anesthetized and unanesthetized normal dogs after intravenous injection of plasma from nephrectomized and normal dogs that have been made hypotensive by controlled hemorrhage. The injection of plasma from nephrectomized, nonhypotensive dogs or the in vitro incubation of normal plasma with calculated proportions of plasma from nephrectomized, hypotensive dogs did not produce any changes in plasma renin concentration or angiotensin production. These results suggest the presence of renin-releasing factor of extrarenal origin which is produced and circulated in the plasma of dogs subjected to periods of hypotension by means of controlled hemorrhage. A direct or indirect action of the renin-releasing factor on the kidney in association with or in conjunction with one or more of the other mechanisms that have been hypothesized to explain the control of renin release is not as yet known. An alternative hypothesis should also be considered. It is possible that the renin-releasing factor may he an activator of the conversion of prerenin to renin and of its release from the kidney into the bloodstream. The source and chemical nature of the renin-releasing factor are not as yet known.

A Plasma Humoral Factor of Extrarenal Origin Causing Release of Reninlike Activity in Hypotensive Dogs