Volume 1, Number 2, June 2000

ACE inhibition and the kidney: species variation in the mechanisms responsible for the renal haemodynamic response
M Cecilia Lansang, Norman K Hollenberg

The mechanisms by which angiotensin-converting enzyme inhibitors (ACE-I) reduce the progression of renal injury in diabetes mellitus and other forms of nephropathy remains unclear, in particular whether the major influence is by inhibition of angiotensin II (Ang II) formation, or by inhibition of kininase II and the consequent potentiation of bradykinin (BK), prostaglandin (PG) and nitric oxide (NO) vasodilatory pathways. In addition, the possibility of important species differences in the pathways by which ACE-I affect the kidneys has been suggested. The current paper makes a systematic review of the published literature. Studies were categorised according to their method of assessing the mechanisms of ACE-I action; some studies measured plasma levels of the relevant hormones after ACE-I administration, whereas others measured haemodynamic responses when ACE-I were administered in conjunction with other drugs, including angiotensin receptor blockers (ARBs) and agents which block BK, PG and NO pathways. Experiments in rat, dog and rabbit were analysed separately and compared with the limited data available in humans. As the analysis proceeded, it became clear that there were obvious similarities between rat and dog and so the results from these species are discussed together in this review.
Overall, the available data suggest important species differences in the mechanisms responsible for the renal haemodynamic response to ACE inhibition. In the rat and dog, there seems to be a substantial contribution from BK-dependent mechanisms. In contrast, in rabbit and humans, only minor contributions are made by this pathway, the major effect being due to a reduction in Ang II formation.

JRAAS 2000;1:119-124.

View full PDF article (open in new window)
Email this article

Right click on this DOI link and copy link to cite this article (What is a DOI link?)