Artikel
The role of renal CYP3A enzymes in the SHR model
CYP3A Iso-Enzyme und ihre Bedeutung für die Hypertonie im SHR Modell
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Autoren
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S. Kain
- Charité - Universitätsmedizin, Campus Benjamin Franklin, Inst. Klin. Pharmakol. Toxikol. Berlin
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J. Bolbrinker
- Charité - Universitätsmedizin, Campus Benjamin Franklin, Inst. Klin. Pharmakol. Toxikol. Berlin
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M. Wehland
- Charité - Universitätsmedizin, Campus Benjamin Franklin, Inst. Klin. Pharmakol. Toxikol. Berlin
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R. Kreutz
- Charité - Universitätsmedizin, Campus Benjamin Franklin, Inst. Klin. Pharmakol. Toxikol. Berlin
| Veröffentlicht: | 8. August 2006 |
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Gliederung
Text
Cytochrome P450 3A (CYP3A) enzymes are playing an important role in drug metabolism in gut and liver. The CYP3A5 isoenzyme is also expressed in the kidney and has been implicated in renal sodium reabsorption and blood pressure regulation in humans. Previously, animal studies in the spontaneously hypertensive rat (SHR) have suggested a link between CYP3A activity and hypertension in this model.
To further elucidate the relation between specific CYP3A isoform expression in the kidney and hypertension, we have analyzed the expression of several CYP3A enzymes in the kidney of male adult SHR animals with established hypertension in comparison to normotensive Wistar Kyoto (WKY) rats (n=6-8, respectively). At present, 6 different CYP3A enzymes have been suggested to be expressed in the rat, i.e. CYP3A1, CYP3A2, CYP3A9, CYP3A18, CYP3A62 and CYP3A21, while the latter has been supposed to be a variant of CYP3A1.
Of these CYP3A enzymes we set our focus on the 4 most frequently described enzymes, i.e. CYP3A1, CYP3A2 CYP3A9, and CYP3A18.
We could confirm the expression of all four enzymes in rat liver, but only CYP3A2, CYP3A9, and CYP3A18 were also expressed in the kidney by qualitative RT-PCR analysis. Subsequent quantification by real-time PCR analysis using an ABI PRISM 7000 SDS instrument showed a significant lower expression of CYP3A9 in the cortex of adult SHR compared to WKY rats (-80%, p<0.05). There were no significant difference in the expression of CYP3A2 and CYP3A18 between SHR and WKY.
These data support the hypothesis that CYP3A enzyme expression in the kidney is involved in blood pressure control. The results are in agreement with our recent analysis in humans indicating a blood pressure lowering effect of renal CYP3A5 expression.
