Article
Transfer of the WKY-ACE locus into a congenic SHRSP strain confirms a strong determination of plasma ACE activity that is independent from hypertension
Die Plasma ACE Aktivität wird genetisch determiniert und ist unabhängig von der Hypertonie
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Published: | August 10, 2005 |
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Objectives: Plasma angiotensin I-converting enzyme (ACE) levels show a genetically determined interstrain variability between the stroke-prone spontaneously hypertensive rat (SHRSP) and the normotensive Wistar-Kyoto (WKY) rat. Thus, plasma ACE levels are twofold higher in WKY compared to SHRSP, while F1-animals derived from both strains show intermediate levels indicating a co-dominant genetic effect. Therefore, the difference between the WKY and SHRSP ACE-alleles mirror the insertion/deletion polymorphism of ACE in humans. We tested the effect of the WKY ACE-allele on blood pressure (BP) regulation in the SHRSP strain.
Methods: We established a congenic strain SHRSP-ACE/WKY for chromosome 10 carrying the ACE locus of the WKY rat on the background of SHRSP. Male rats of each strain were studied at the age of sixteen weeks. BP was measured over a period of 14 days by radiotelemetry (n=6 each). Plasma ACE levels were studied by enzymatic activity measurements (n=12 each).
Results: Total genome scan analysis confirmed the purity of the congenic strain outside the ACE-locus. Plasma ACE activity in WKY (223.53 +/-46.01 U/l) and congenic SHRSP-ACE/WKY animals (198.60 +/- 63.56 U/l) were similar and significantly elevated compared to SHRSP (89.75 +/-20.1, p<0.01). Despite the twofold elevated ACE levels systolic BP showed no significant difference in SHRSP-ACE/WKY (234 +/- 16 mmHg) compared to SHRSP (235 +/- 7 mmHg) and thus a similar elevation compared to WKY (124 +/- 6 mmHg) (p<0.0001).
Conclusion: Our data confirm a strong genetic determination of plasma ACE levels, which are not modulated by BP and do not affect the severe hypertension in SHRSP.