Release of a renin-like enzyme from the pregnant uterus of the rabbit

Gross, Schaechtelin, Ziegler & Berger (1964) and Ferris, Gorden & Mulrow (1967) have reported that homogenates of pregnant rabbit uterus contain a renin-like enzyme.The enzyme resembles renin in terms of resistance to moderate acidification and precipitation at half-saturation with ammonium sulphate.When injected intravenously itcauses a prolonged rise of mean arterial blood pressure, and when incubated with renin-substrate it releases an angiotensin-like polypeptide.Although it remains to be determined whether the uterine enzyme is identical with renal renin, the fact that the enzyme releases an angiotensin-like polypeptide may be of first importance.As discussed by Braun-Menendez (1956) and Peart (1965), all known pharmacological actions of renin appear to be mediated through the release of angiotensin.Renin reacts with renin-substrate to formthe decapeptide, angiotensin I, and angiotensin I is hydrolysed by converting enzyme into the octapeptide, angiotensin II, before its biological effects are exerted (Skeggs, Lentz, Kahn, Shumway & Woods, 1956; Lentz, Skeggs, Woods, Kahn & Shumway, 1956; Peart, 1956; Elliott & Peart, 1957).Therefore it follows that any enzyme capable of hydrolysing renin-substrate to form angiotensin I or II under conditions that prevail in vio mayhave pharmacological actions like renal renin.The fact that homogenates of pregnant rabbit uterus contain a renin-like enzyme does not indicate that the enzyme behaves physiologically or pathologically like renal renin.On present evidence it can be argued that the enzyme has the specificity but may not have the opportunity of hydrolysing renin-substrate in vivo.The enzyme may be without effect unless released into a tissue space (e.g.vascular or lymphatic) containing renin- substrate and converting enzyme at a pH suitable for the formation of angiotensins I and II.To determine if the uterine renin-like enzyme can be released, we have looked for renin-like activity in the effluent of the pregnant rabbit uterus perfused in vitro.Rabbits 28 days pregnant were anaesthetized with intravenous pentobarbitone (30mg./kg.) and the uterus was approached through a midline incision.A uterine vein was cannulated and then perfused against the flow to outline the uterine segment drained by the vein.The identified segment was excised, cut along its lateral aspect, and the foetus and placenta were