Renin in Experimental Renal Hypertension in Monkeys

Abstract

1. Monkey renin and human renin, but not hog, dog, or rabbit renins, were pressor in the monkey. Monkey renin was neutralized by antirenin to human renin, but not by antirenin to hog renin or antirenin to dog renin. 2. Experimental renal hypertension developed consistently in the monkey after unilateral 3:1 renal artery constriction and became more marked after contralateral constriction or nephrectomy. Hypertension usually persisted when the second kidney was left untouched. 3. Chronic experimental renal hypertension in the monkey was treated with partial success by crude human renin. Semipurified hog renin was not therapeutically effective. 4. Chronic experimental renal hypertension was treated successfully by passive administration of dog serum containing antirenin to human renin, but not by dog serum containing antirenin to hog renin or dog serum without antirenin. 5. Prophylaxis of experimental renal hypertension with crude human renin was partially successful in preliminary experiments. 6. Attempts to alter the antigenicity of hog renin through chemical treatment so that the antibody to it would neutralize human renin were not successful. Antihypertensive effects were not observed during treatment or prophylaxis experiments with chemically treated semipurified hog renin. 7. The interfering effects of renal medulla seen in the treatment of renal hypertension in dogs with hog renin were not observed in monkeys treated with human renin. 8. During each individual experiment involving treatment of the renal hypertensive monkey with human renin, correlation was observed between the extent of the antihypertensive response and the antirenin titer to human renin. On the other hand, correlation was not apparent when the antihypertensive response and the maximum antirenin titers of different experiments were compared. However, rough correlation between antihypertensive responses and maximum antirenin titers was observed in passive administration experiments with antirenin to human renin. 9. Passive administration of dog serum containing antirenin to human renin to renal hypertensive monkeys was followed by antihypertensive responses which were substantially more marked than in monkeys in which comparable antirenin titers were produced by daily injections of human renin. Passive administration of normal dog serum or dog serum containing antirenin to hog renin was not followed by decreases in blood pressure during initial experiments with dog serum. Sensitization to dog serum was a complicating feature of passive administration experiments after the initial experiment. 10. With both active and passive treatment, the minimum titers of antirenin to human renin required for minimal antihypertensive responses in the monkey were lower than the minimum effective titers of antirenin to hog renin observed previously in dogs. 11. The chief postoperative complication after renal artery constriction in the monkey was congestive heart failure. Malignant hypertension with necrotizing arteriolar lesions occurred infrequently. Atherosclerosis and cardiac hypertrophy were common findings after a year or more of hypertension. Arteriolar lesions were absent or minimal. Significant nephrotoxic effects did not appear to result from daily injections of crude human renin or from passive administration of dog serum containing antirenin to human renin. 12. These results support the hypothesis that renin (or a closely related protein) plays a role in the pathogenesis of primate experimental renal hypertension. 13. Passive administration experiments with antirenin to human renin to determine the possible role of renin in the pathogenesis of essential hypertension are a practical possibility.