Does renal sodium handling modulate the secretion of active and inactive renin?

Lush, David Joseph (1980) Does renal sodium handling modulate the secretion of active and inactive renin? University of Southampton, Doctoral Thesis.

Abstract

The renin-angiotenein system is intimately involved in the homeostasis of extracellular fluid volume, total body sodium and blood pressure. The overall expression of this system is initially related to the secretion of renin from the kidney. However, it is now known that inactive, but activatable, forms of renin exist in the plasma and kidneys of many species and it has been proposed that differential secretion of active and inactive renins could represent a further point of control in the renin-angiotensin system. Changes in the relative proportions of the two forms of plasma renin appear to be linked to a 'sodium sensitive' receptor, possibly at the macula dense. Diuretic-induced secretion of active and inactive renin was investigated using conscious sheep with chronically implanted artery, vein and bladder catheters. Effects of anaesthetic agents on renal function and renin secretion were therefore avoided. Volume depletion, as a result of the diureais was obviated. Furosemide, at two dose levels, produced large changes in renal function but no change in plasma active or inactive renin in the conscious sheep. However, furosemide increased plasma active reninin anaesthetised animals. Inactive renin, compared to control animals, was reduced concurrently. Further investigation in conscious sheep revealed that plasma active renin increased, and inactive renin relatively decreased, following furosemide administration during an infusion of papaverine. The osmotic diuretic mannitol, when given to conscious volume replete sheep, produced a moderate reduction in plasma active renin with no apparent effect on inactive renin. The mainly renal origin of both forms of renin was indicated by an 85% drop in plasma renin activity following nephrectomy. Studies on the in vitro secretion of active and inactive renin from sheep renal cortical slices demonstrated that changes in medium sodium or potassium had little effect on secretion of either form of renin. Active renin release was also unresponsive to adrenergic agonists, and relatively unresponsive to pentobarbital. Drug-induced decreases in the amount of inactive renin did, however, occur. Interpretation of these results was not assisted by reviewing previous, often conflicting, reports. Preliminary studies indicated that sodium depletion, induced by peritoneal dialysis of the conscious or anaesthetised rabbit, increased plasma active renin with a decrease in the proportion of total reninwhich was inactive. The major conclusion from this thesis is that the widely reported macula dense mechanism for the control of renin release does not play a primary role in the intact, conscious sheep. Only when an additional factor such as anaesthesia, vasodilation or volume depletion is superimposed do changes in renal sodium handling increase active and decrease inactive renin secretion.

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