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In isovolemic cross-circulation experiments, a nephrectomized donor rat, into which various doses of hog renin were injected, was connected to a nephrectomized indicator rat. The blood pressure increase thus produced in the indicator rat was compared with the blood pressure response obtained during cross circulation using either intact normotensive or renal hypertensive rats as donor animals. An exponential dose-response relationship was found between hog renin injected into a nephrectomized donor and the blood pressure increase of the indicator rat. Using the cross-circulation technique, the disappearance rate of endogenous reninlike material in the blood of donor animals and of exogenous renin injected into nephrectomized donor animals was examined. If an intact normotensive animal or a unilaterally nephrectomized hypertensive animal is totally nephrectomized, reninlike material disappears from the blood within 1 hr. In renal hypertensive rats with an untouched contralateral kidney which have a higher concentration of reninlike material in the blood, it takes about twice the normal time until reninlike material disappears from the blood after nephrectomy. The increased and prolonged blood pressure response of the nephrectomized animal to renin is not connected with a prolonged persistence of renin in the blood.

No abstract

The effect of different chemical reagents on renin has been investigated. After treatment of hog renin with acetic anhydride, 1-fluoro-2,4-dinitrobenzene, diazobenzene sulfonic acid and phenyl isocyanate, the enzymic activity assayed both biologically and chemically was depressed, whereas no effect occurred after treatment with diisopropyl fluorophosphate, p-chloromercuribenzoate and after dialysis against EDTA. Human renin, too, is inactivated by acetylation, diazo coupling and dinitrobenzoylation. The results indicate that one or several amino groups of the renin molecule are essential for enzymic activity.

The renin-like pressor material present in blood under various experimental conditions was determined by isovolemic cross circulation using nephrectomized rats as assay animals and rats having different concentrations of renin in the kidney as "donor" animals. Cross circulation was established by connecting the femoral arteries of both animals with the corresponding femoral veins and maintaining a constant flow. In intact anesthetized rats, a "basic" concentration of renin-like pressor material is demonstrable in the blood which is not influenced by unilateral nephrectomy. In the rat made hypertensive by clamping one renal artery, leaving the other kidney untouched, an increase in circulating renin-like pressor material is demonstrable. In unilaterally nephrectomized rats in which the artery of the remaining kidney is clamped, the concentration of circulating pressor material is not elevated. In adrenalectomized rats, an increase of circulating pressor material coincides with an elevated concentration of renin in the kidneys. There is a good correlation between the concentration of renin in the kidney and of pressor material in the blood, while the level of circulating renin-like substance is not correlated with the height of blood pressure.