Investigations into the effects of angiotensin converting enzyme inhibition and anaesthesia on renin release

Parker, Jane Caroline (1986) Investigations into the effects of angiotensin converting enzyme inhibition and anaesthesia on renin release. University of Southampton, Doctoral Thesis.

Abstract

The renin-angiotensin system is involved in maintaining blood pressure and in the regulation of salt and water balance. Regulation may result from alterations in the relative release of active and inactive renin from the kidney. This hypothesis has been investigated in this thesis using conscious sheep with chronically implanted femoral artery, vein and bladder catheters. Plasma levels of both forms of renin can vary but not necessarily in parallel or at the same rate. Enalapril, a converting enzyme inhibitor which blocks angiotensin II formation, led to an increase in both forms of plasma renin but a delay preceded changes in inactive renin. A marked drop in blood pressure also occurred. The kallikrein-kinin and protaglandin systems could be involved in these responses since angiotensin converting enzyme is synonymous with kininase II. The kallikrein inhibitor aprotinin had no effect on basal renin release but selectively attenuated the enalapril-induced increase in plasma inactive renin concentrations. Kallikreins have been suggested to activate inactive renin in vivo but no evidence of this was seen in these experiments. Indomethacin, a prostaglandin synthesis inhibitor, selectively reduced plasma active renin only in both basal and enalapril-stimulated release. Blocking β-adrenoceptor-mediated renin release with atenolol lowered inactive renin to a greater extent than active renin and, after enalapril administration, the increase in both plasma active and inactive renin levels was attenuated. It is concluded that prostaglandins and a β-adrenoceptor mediate the increases in secretion of both forms of renin produced by enalapril, though by different mechanisms. Loss of the inhibiting feedback by angiotensin II is therefore not the sole mechanism involved in promoting renin release by these drugs. Pentobarbitone anaesthesia was shown to alter the response of the kidney to experimental manipulations. With pentobarbitone only plasma active renin levels increased, which increase was inhibited by prior treatment with indomethacin. Enalapril in anaesthetised animals led to enhanced increases in both forms of renin, an effect which was also attenuated by pretreating the animals with indomethacin. This shows that pentobarbitone has a marked effect on the renin system, probably via direct stimulation of prostaglandin synthesis. In vitro studies showed that pentobarbitone also affected basal inactive renin release via a prostaglandin-sensitive mechanism. In anaesthetised animals, therefore, the response of the renin-angiotensin system to experimental manipulations is markedly different from that in conscious animals. Relatively few studies have looked at the independent control of active and inactive renin secretion. Alteration of the renin system by a variety of drugs shows that the secretion of the two forms of renin can be selectively altered and can follow a different time course. Control of activation of inactive renin may form the basis of a new control site in the renin system. (D74416/87)

This record has no associated files available for download.

Contributors

Download statistics