Pathophysiological roles of vascular 11beta-hydroxysteroid dehydrogenase and aldosterone.
Mineralocorticoid receptor (MR) binding is tightly regulated by the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSDII) which selectively metabolizes glucocorticoids to inactive metabolites, thus allowing for MR activation by aldosterone. To examine whether this enzyme is involved in the pathophysiology of salt-sensitive hypertension, 11beta-HSDII activity and messenger RNA (mRNA) levels were determined in blood vessels of Dahl Iwai salt-sensitive (DS) and salt-resistant (DR) rats. Decreased 11beta-HSDII activity and mRNA levels in mesenteric arteries were observed in 8-week-old DS rats on a high-salt diet, indicating that 11beta-HSDII may play a significant role in salt sensitivity and hypertension. It has been suggested that mineralocorticoids act on blood vessels, leading to increased vasoreactivity and peripheral resistance. We present direct evidence that blood vessels are aldosteronogenic. The production of aldosterone in blood vessels was compared between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. Vascular aldosterone and CYP11B2 mRNA levels were significantly increased in 2-week-old SHRSP versus WKY rats. However, the vascular aldosterone levels in 4- and 9-week-old SHRSP and WKY rats were similar. High sodium intake further increased both blood pressure and vascular aldosterone synthesis in the SHRSPs. Both the local renin-angiotensin-aldosterone system (RAAS) and the vascular 11beta-HSDII level are critically important in the pathophysiology of cardiovascular disorders.
Takeda
Yoshiyu
Y
Molecular Genetics of Cardiovascular Disorders, Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa University, Kanazawa 920-8641, Japan. takeday@im2.m.kanazawa-u.ac.jp
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D001794:Blood Pressure; D015971:Gene Expression Regulation, Enzymologic; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology / Q000503:physiopathology*; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000494:pharmacology
D012333:RNA, Messenger; D012982:Sodium, Dietary; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases