Renal Hyperemia Induced in Man by a New Phthalazine Derivative

Pyrogen is the only substance which has been reported to increase significantly the renal blood flow in man. However, according to Goldring and Chasis, 1 it is not suitable for therapeutic purposes. Aminophylline seems to be effective only in patients with cardiac failure. 2 No treatment which will relieve renal ischemia has yet been found. According to Meier et al., 3 Compound 5968 (hydrazino-phthalazine hydrochloride), supplied by Ciba, produces in animals a sustained fall in blood pressure. In man, we found that hypotension did not occur regularly following the subcutaneous injection of 10 mg. However, when measurements of renal plasma flow were performed, using the clearance technic, 1 it became evident that renal hyperemia could be elicited in nearly every subject. A similar effect has also been demonstrated in cats by thermostromuhr measurements. 3 Our data, presented in Table I, demonstrate that this drug can cause increase in renal plasma flow in man varying from 16 to 68%, averaging 38.6%. The glomerular filtration rate, as reflected by the clearance of thiosulphate, is not consistently affected. The filtration fraction is always decreased. In some cases, urine volumes are markedly increased. Blood pressure shows a definite reduction only in some hypertensive patients. Therefore, the influence of the drug upon the kidney is somewhat similar to that of pyrogenic substances. The responses obtained are moderately prolonged, lasting 1 to 2 hours or more. Toxic manifestations are relatively unimportant. Moderate tachycardia may be observed in some cases. Effects of the drug upon cardiac output are being investigated. From these results, it can be concluded that the drug 5968 (Ciba) is a renal vasodilator in man.