Background: To study the regulation of a naturally occurring genetic variant of high angiotensin-converting enzyme (ACE) gene (Ace in rat) expression, i.e., the Ace allele of the normotensive Wistar-Kyoto (WKY) rat, in the hypertensive background of stroke-prone spontaneously hypertensive (SHRSP) rats. Methods: We analyzed a congenic strain termed SHRSP.WKY-Ace derived from SHRSP in which a chromosomal fragment of rat chromosome 10 including Ace was replaced by the WKY locus. We compared blood pressures by radiotelemetry, measured plasma ACE activity, tissue ACE messenger RNA (mRNA) and enzyme activities in lung, kidney, and left ventricle (LV) of the heart in adult animals. Results: Congenic animals demonstrated a twofold increase in plasma ACE activity in comparison to SHRSP (P < 0.05) and thus similar levels to WKY. The increased tissue expression of ACE mRNA and enzyme activities in lung, kidney, and LV observed in WKY were similarly found in congenic animals when compared to SHRSP (P < 0.05, respectively). Systolic and diastolic blood pressures were not different between congenic and SHRSP animals. Analysis of renin in plasma and angiotensin peptides in LV tissues indicated the induction of compensatory mechanisms by downregulation of renin and angiotensin I (Ang I) concentrations in congenic animals. Conclusions: We demonstrated that genetically determined high ACE expression linked to WKY Ace remains unchanged in the hypertensive background of SHRSP.WKY-Ace. Our data indicate that buffering mechanisms in the renin-angiotensin system contribute to the finding that the development of spontaneous hypertension is not affected, despite an average twofold higher expression of ACE in congenic animals.,
American Journal of Hypertension
Department of Internal Medicine

Nassar, I., Schulz, A., Bernardy, C., Garrelds, I., Plehm, R., Huber, M., … Kreutz, R. (2008). A twofold genetic increase of ACE expression has no effect on the development of spontaneous hypertension. American Journal of Hypertension, 21(2), 200–205. doi:10.1038/ajh.2007.38