These experiments indicate that, in dogs at least, ischemia localized to the kidneys is a sufficient condition for the production of persistently elevated systolic blood pressure. When the constriction of both main renal arteries is made only moderately severe in the beginning, the elevation of systolic blood pressure is unaccompanied by signs of materially decreased renal function. In this respect the hypertension in these animals resembles the hypertension which is associated with so called benign nephrosclerosis in man. Subsequent increase of the constriction of the main renal arteries does not materially damage renal function, probably because of adequate development of accessory circulation. More delicate methods for detecting a change may yet prove that some damage does occur. Almost complete constriction of both main renal arteries, from the beginning, results in great elevation of systolic blood pressure which is accompanied by severe disturbance of renal function and uremia. This resembles the type of hypertension which is associated with so called malignant nephrosclerosis, in the sense of Fahr (17). In several of the animals with persistent elevation of systolic blood pressure, anatomical changes were observed in the glomeruli, vessels and parenchyma of the kidneys which are most probably directly referable to the ischemia. It is hoped that these investigations will afford a means of studying the pathogenesis of hypertension that is associated with renal vascular disease.

A method has been described for the production of hypertension in dogs by the constriction of the main renal artery of one or both kidneys (2, 3). When the main renal artery of only one kidney is constricted, the blood pressure rises, but after a variable period returns to the original level. When both main renal arteries are adequately constricted, or if one is constricted and the other kidney is removed, the blood pressure usually remains elevated. This has been accomplished successfully in dogs (3) and in monkeys (4), and the method, or some modification of it, has now been used by ourselves (2-11) and others (12-93) in the production of hypertension by renal ischemia and in the investigation of the pathogenesis and treatment of this type of hypertension, as well as the application of the results to the problem of human hypertension.In small laboratory animals, like monkeys, cats, rabbits and rats, it is rather di~cult to constrict adequately without frequently occluding the main renal artery. It occurred to us that if moderate constriction of the aorta just above the origin of both main renal arteries would result in hypertension, at least above the site of the damp, and if constriction immediately below the origin of the renal arteries would have no effect on the blood pressure, this would indicate that

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The disadvantages of repeated subcutaneous insulin injections in the treatment of diabetes mellitus are well known. Numerous attempts have been made to find a more satisfactory route, which have largely centered around absorption from mucous surfaces. Generally the results have been uncertain, uneconomical, and at times impracticable, in spite of alterations in insulin and its use in combinations with other substances. There are many excellent reviews in the literature covering this subject, and one especially complete by Stammers (1).There is no reference in the literature concerning absorption of insulin from the conjunctival membranes. Success by this route would obviate certain of the major objections to the hypodermic method. The animal experiments herewith reported have been carried out to determine the practicability as to rate, duration and constancy of absorption of insulin usage by the instillation of it in the conjunctival sac. Such instillation cannot be made in animals without waste, which should not occur in man, so it is therefore impossible to give accurate quantitative expression to the relative effectiveness of insulin by this route as compared to the subcutaneous injections. It is felt that more accurate data as to the economic possibilities of this method can best be determined by actual studies on human diabetics. We are now engaged in such studies. For our work in the clinic we have started with dry insulin, dissolving it in a menstrum, which both lessens the high pH of commercial insulin and frees it from phenol, which we believe makes it absolutely safe for conjunctival instillation. In addition we have developed a dropping device which eliminates the danger of trauma to the eye and measures the dose with fair accuracy.

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