Activation by puff adder venom of inactive renin in normal and hypertensive rat plasma

Inactive renin has been studied extensively in human plasma, but in animal plasma its accurate quantification has proved more difficult, due partly to higher activity of plasma protease inhibitors. Such activity in human plasma can be conveniently destroyed by a metalloprotease in Bitis arietans venom, with concommitant release of endogenous enzyme activities, such as plasma kallikrein, that then activate inactive renin. It was therefore of interest to look for inactive renin in rat and rabbit plasma using this approach, so providing, in addition, a comparison for the disparate data of other groups who have used trypsin or acid for activation. In both rat and rabbit plasma the proportion of inactive renin was 62% of total renin, whereas human plasma contained more inactive renin and a higher proportion, 82%. A higher concentration of venom was required for rat (33 ug venom/ml plasma) and rabbit (4 micrograms/ml) than needed for activation, at a similar rate, in human plasma (1 microgram/ml). When applied to studies of rats made hypertensive and hyper-reninaemic by aortic ligation for 5 days, higher total (active + inactive) renin was observed. The proportion of inactive renin, as a percentage of total renin in plasma collected at this time, was, however, found to diminish significantly. In conclusion, puff adder venom activates inactive renin in rat and rabbit plasma and can be used to study physiological changes in inactive renin in such animal plasma.