Inactive renin: investigations of a novel physiological control step for renin system using conscious sheep

Abstract

The renin-angiotensin system is involved in maintaining blood pressure and in the regulation of salt and water balance. Overall regulation of the renin system could partially be effected through alterations in the relative rates of secretion of active and inactive forms of renin from the kidney. This thesis describes work which investigated this hypothesis, using conscious volume replete sheep with implanted artery, vein and bladder catheters.
It was found that plasma levels of the two forms of renin did not necessarily change in parallel. Infusion of the β-adrenoceptor agonist, isoprenaline, increased plasma active renin, a response which could be suppressed with the β blocker propranolol. Isoprenaline, initially, had no effect on inactive renin but, subsequently, a decrease was recorded. Propranolol selectively suppressed basal plasma inactive renin.
The calcium antagonist, verapamil, increased both active and inactive renins in plasma but a peak response was attained after 45 min and, despite continued infusion of verapamil, both forms of renin had returned almost to control levels 2 1/2 hr after starting drug administration.
Other studies using two converting-enzyme inhibitors, captopril and enalapril (MK. 421), demonstrated that these drugs increased active and inactive renin in parallel. It is concluded that the feedback inhibition of renin release by angiotensin II suppresses both forms of renin equivalently.
Anaesthesia alters the response of the kidney to experimental manipulations. In conscious sheep, haemorrhage (10% of calculated total blood volume) increased both active and inactive renin. A maximum mean increase of 72% for active and 86% for inactive renin was recorded. However, in pentobarbitone-anaesthetized sheep the same level of haemorrhage increased plasma active renin by 303% and inactive renin by 299%.
Acidification was used to activate inactive renin so that it could be assayed. An attempt was made to identify conditions for reproducible activation of sheep inactive renin by trypsin. But these studies failed to provide any evidence that this would be a viable alternative to acid activation.
The major conclusion from this thesis is that differential secretion of active and an inactive, but activatable, form of renin forms the basis of a new control step in the renin angiotensin system.

More information

Identifiers

Catalogue record

Export record