Renal 11beta-hydroxysteroid dehydrogenase in genetically salt-sensitive hypertensive rats.
-Renal 11beta-hydroxysteroid dehydrogenase II (11beta-HSDII) converts glucocorticoids into inactive metabolites and plays an important role in controlling blood pressure and sodium retention. To examine whether this enzyme may be involved in the pathophysiology of salt-sensitive hypertension, we determined 11beta-HSDII activity and mRNA levels in the blood vessel and kidney of Dahl Iwai salt-sensitive (DS) rats and Dahl Iwai salt-resistant (DR) rats. Urinary free corticosterone:free 11-dehydrocorticosterone ratio was measured to estimate renal 11beta-HSD activity. Vascular 11beta-HSDII activity was expressed as percent conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone in homogenized mesenteric arteries. 11beta-HSDII mRNA was estimated with the use of competitive polymerase chain reaction (PCR). Renal 11beta-HSDII activity and mRNA levels were significantly decreased in 8- and 12-week-old high salt DS rats compared with DR, Sprague-Dawley (SD), or low salt DS rats of the same age. Decreased 11beta-HSDII activity and mRNA levels in mesenteric arteries were observed in 8- and 12-week-old high salt DS rats. Urinary excretion of 11beta-HSDII inhibitory factors was measured by inhibition of enzyme activity in microsomes from human kidney. The urinary inhibitors were significantly increased in 8- and 12-week-old high salt DS rats compared with DR, SD, or low salt DS rats of the same age. There were no significant differences in 11beta-HSDII activity and mRNA levels in mesenteric arteries and kidney or in urinary inhibitors between 4-week-old DS, DR, and SD rats. These results indicate that 11beta-HSDII may play a role in salt sensitivity and development of hypertension in the DS rat.
Takeda
Y
Y
Second Department of Internal Medicine and Department of Health Sciences, School of Medicine, Kanazawa University, Japan. takeday@mhs.mp.kanazawa-u.ac.jp
Inaba
S
S
Furukawa
K
K
Miyamori
I
I
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D004791:Enzyme Inhibitors / Q000652:urine; D015870:Gene Expression; D006439:Hemodynamics; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006973:Hypertension / Q000097:blood / Q000201:enzymology* / Q000652:urine; D007668:Kidney / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D013997:Time Factors
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases