Inactive renin : a new site for control of the renin-angiotensin system?

Richards, Hugh Kenvyn (1980) Inactive renin : a new site for control of the renin-angiotensin system? University of Southampton, Doctoral Thesis.

Abstract

The renin-angiotensin system plays a central role in the maintenance of extracellular fluid volume, total body sodium and blood pressure. In recent years it has become increasingly evident that control of the renin-angiotensin system is achieved at several points rather than solely by the control of renin secretion. Activation of an apparently inactive, but activatable, form of renin is one such possibility. Inactive renin has been described in the kidney and plasma of several species, but very little is known about its physiological role. This was investigated in the work described in this thesis. Both active and inactive renins were measured simultaneously in the plasma of the anaesthetized rabbit and the effect of several experimental procedures was investigated. Inactive renin was found to represent 1520% of total plasma renin. When active renin release from the kidney was stimulated by acute haemorrhage or close renal artery infusion of isoprenaline, there was no change in the relative proportions of the two forms of renin. On the other hand, when renin release was stimulated by administration of furosemide, inactive renin completely disappeared from the circulation. Renin release from rabbit kidney cortex slices was also investigated. Once again it was found that inactive renin represented 15-209 of total renin released by control slices. Lowering the sodium concentration in the incubation medium stimulated active renin release, but no inactive renin could be detected. Addition of furosemide to the incubation medium neither stimulated active renin release nor changed the proportions of active and inactive renins. This indicated that the action of furosemide inhibiting secretion of inactive renin in vivo is mediated by some aspect of renal function. Isoprenaline, when added to the incubation medium, stimulated renin release with no change in the relative proportions of active and inactive renin. It is suggested that activation of inactive renin or its secretion from the kidney is linked to some aspect of the renal handling of sodium. Stimulation of renin release by intrarenal baroreceptor or p-adrenoceptor mechanisms is not associated with any activation or differential secretion of inactive renin. Results from in vitro studies indicate that the control of plasma inactive renin is predominantly an intrarenal event. Evidence for a new site for control of the renin-angiotensin system is therefore presented.

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