AN EXPERIMENTAL INVESTIGATION INTO HYPERTENSION OF RENAL ORIGIN, WITH SOME OBSERVATIONS ON CONVULSIVE "URÆMIA."

¹ Pharmacology Laboratory, Cambridge

1. Hypertension has been produced in dogs by obstructing the blood-supply to their kidneys by a modification of Goldblatt's technique. Measurement of the arterial pressure was made by the application of a specially designed cuff to the van Leersum loop, the ipselateral carotid sinus having been denervated.

2. The time-course of the blood-pressure changes, and its correlation with structural alterations in the kidneys have been investigated. Results obtained from (a), obstruction of one renal artery only, followed later by the removal of the ischaemic kidney, (b) from complete nephrectomy, and (c) from the production of renal insufficiency in the absence of ischaemia, have led to the conclusion that the presence of ischaemic renal tissue is an indispensable condition for the development of hypertension.

3. The time-course of development and disappearance of hypertension have been measured by a method which disposes of interference by surgical procedures under general anæsthesia.

4. In confirmation of the work of others, the ischæmic kidney was found to produce hypertension even if completely denervated. It undoubtedly did so, therefore, by the formation of some substance which escaped into the general circulation.

5. Sympathectomised dogs reacted like normal dogs to obstruction of their renal arteries. Any action of the hypertensive substance involving stimulation of the sympathetic chains or of the central connections of the sympathetic system was thus excluded.

6. Experiments in which an isolated kidney and a loop of small intestine were each perfused by a heart-lung preparation have shown that the perfused kidney liberates a substance which produces vasoconstriction in the gut. It is assumed as a working hypothesis that this phenomenon is related to the hypertension observed in the whole animal under the conditions of renal ischaemia.

7. The sensitivity of hypertensive dogs to injected adrenaline was occasionally, that to tyramine more regularly increased, whereas decrease in the normal sensitivity to tyramine accompanied the hypertension produced by a constant infusion of tyramine. This and other evidence favour the view that the hypertension which accompanies renal ischsemia is not produced by excess tyramine in the circulation.

8. The reactivity of the carotid sinuses was unaltered in the hypertensive dogs.

9. Removal of one kidney after earlier obstruction of both renal arteries resulted in a further rise of pressure. The same held if, after obstruction of one renal artery only, the sound kidney was removed. Increased load, therefore, raised the hypertension level, even if the amount of ischaemic tissue remained the same or was diminished.

10. Increased dietary loads elicited reversible rises in the bloodpressure level of hypertensive dogs. In the dosage given, urea and meat were found equally potent; sodium chloride was still more effective. Excess of sodium chloride produced cedema in one dog, and convulsive "uraemia" in another.

11. Whein interference with the renal blood-supply was very severe, a syndrome resembling that known as convulsive uramia in man was observed. This was also seen in sympathectomised animals. The frequency of its association with hypertension is probably due to there being a common uniderlying cause (ischaemia) for both phenomena and not to their causal connection. Evidence is presented for the view that convulsive "ursemia" does not develop in the absence of ischaemic or ansemic renal tissue.

Note:

Grateful acknowledgment is made to the Rockefeller Foundation and to the Royal Society for grants in aid of the work described in this paper. The early part of the work was undertaken during the tenure by one of us (M. V.) of a Travelling Fellowship of the Rockefeller Foundation. We would also express our gratitude to the Hirnforschungsinstitut, Neustadt (Director, Professor O. Vogt), for facilities given in the histological preparation of material derived from this investigation.