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11Beta-hydroxysteroid dehydrogenase in the Dahl rat
R Franco-Saenz1, Y Tokita, S Latif
1Department of Medicine, Medical College of Ohio, Toledo, 43699, USA.
American Journal of Hypertension
|November 5, 1997
Summary
Dahl salt-sensitive rats show lower 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity in the liver and kidney. This diminished enzyme activity may contribute to salt sensitivity and hypertension development in these rats.
Area of Science:
- Physiology
- Biochemistry
- Hypertension Research
Background:
- Dahl salt-sensitive (Dahl-S) rats exhibit early-onset hypertension.
- The precise mechanisms underlying salt sensitivity in Dahl-S rats remain unclear.
- 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isoforms regulate mineralocorticoid receptor activity; 11beta-HSD2 deficiency is linked to sodium retention and hypertension.
Purpose of the Study:
- To investigate the activity of hepatic and renal 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in Dahl-S and Dahl-R rats.
- To correlate 11beta-HSD1 activity with the development of hypertension and salt sensitivity in Dahl-S rats.
Main Methods:
- Measurement of hepatic and kidney 11beta-HSD1 activity in Dahl-S and Dahl-R rats at 6 and 10 weeks of age.
- Assessment of plasma renin concentration, aldosterone, and corticosterone levels.
- Monitoring of systolic blood pressure (SBP) in both rat strains.
Main Results:
- Hepatic 11beta-HSD1 activity was lower in Dahl-S rats at 6 weeks (P < .02).
- Renal 11beta-HSD1 activity was significantly lower in Dahl-S rats at 10 weeks (P < .001).
- Dahl-S rats displayed lower plasma renin concentrations and significantly elevated SBP compared to Dahl-R rats at 10 weeks.
Conclusions:
- Dahl-S rats exhibit reduced hepatic 11beta-HSD1 activity early in life and reduced renal 11beta-HSD1 activity as hypertension develops.
- These findings suggest that decreased 11beta-HSD1 activity in both the liver and kidney may play a role in the salt sensitivity and hypertensive phenotype of Dahl-S rats.
