Interstrain differences in angiotensin I-converting enzyme mRNA and activity levels. Comparison between stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats.
Plasma angiotensin I-converting enzyme (ACE) levels are different between the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar-Kyoto (WKYHD) rat. This interstrain variability in plasma ACE levels is independent of blood pressure and is genetically linked to the ACE gene. The present study explored the hypothesis of an interstrain variability of tissue ACE activity and ACE gene expression levels. Tissue ACE levels were studied by enzymic activity measurement in the membrane fraction, and ACE mRNA levels were quantified by solution hybridization-ribonuclease protection assay. In lung, heart, kidney, and duodenum, membrane-bound ACE activity and ACE mRNA amount were significantly higher in WKYHD rats compared with SHRSPHD rats. No difference was observed in the testis where a specific isoform of the enzyme is produced. Our results suggest that in addition to determine differential plasma ACE levels between the WKYHD and SHRSPHD strains, the interstrain genetic variability also determines differential ACE mRNA and membrane-bound enzyme levels in somatic tissues. This likely reflects a difference in the ACE gene expression due to genetically determined regulatory mechanisms operative in all somatic tissues.
Costerousse
O
O
Institute of Clinical Pharmacology, Universitätsklinikum Benjamin Franklin, Berlin, Germany.
Lindpaintner
K
K
Paul
M
M
Ganten
D
D
Kreutz
R
R
D000818:Animals; D015415:Biomarkers; D002561:Cerebrovascular Disorders / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D004386:Duodenum / Q000201:enzymology; D015870:Gene Expression; D014644:Genetic Variation; D006352:Heart Ventricles / Q000201:enzymology; D006973:Hypertension / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D015415:Biomarkers; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A