Observations on the Vasodilator Properties of Urine

Abstract

These experiments trace the recent interest in the vasodilator properties of urine. This interest was triggered by the incidental observation of a potent coronary dilator influence when urine was introduced into the reservoir of the isolated supported heart preparation. A comparison of human urine with nitroglycerin then revealed that 10 ml. of urine had 2 to 3 times the dilator potency of 0.6 mg. nitroglycerin. Neither agent altered myocardial oxygen consumption or efficiency at the peak of their effect. The development of a simple, rapid and reproducible bioassay technic which would permit the comparative examination of numerous samples in the same preparation was a necessary precursor to realizing the broader objective of ascertaining whether the vasodilator substance in urine has physiologic significance for circulatory regulation. Accordingly, a re-examination was made of the limitations of the femoral arterial flow technic. The irregularity in the amplitude and contour of sequential responses to the same test substance in spite of an apparently steady hemodynamic state suggested the possibility of inadequate mixing after injections into the external circuit. Model studies with blue dye confirmed this impression and a magnetic mixer was therefore introduced into the external circuit in order to thoroughly mix the injected material. This resulted in substantially improved reproducibility and the obtaining of satisfactory dose-response curves. This technic was then used to assay the 24 hour output of vasodilator activity in the urine of 5 hypotensive patients and 5 normal individuals. The hypotensive group exhibited something less than 15 per cent of that secreted by the control group. The substance under examination is non-dialyzable and, chemically, resembles callicrein. The urines from 9 mammalian species all exhibited high activity. These observations were construed as being compatible with the hypothesis that the vasodilator agent under examination is, in some way, associated with autonomic function and/or the regulation of arterial pressure. This view was supported by the observation of a diminished vasodilator output in the sheep while under the influence of ganglionic blockade with hexamethonium.