Vascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells.
Mineralocorticoids have been suggested to act on blood vessels, leading to increased vasoreactivity and peripheral resistance. However, the site of their production has so far been believed to be only the adrenal cortex. Here, we show direct evidence that vascular cells per se are aldosteronogenic, possessing their own system that responds to the steroid. Using polymerase chain reaction after reverse transcription, the CYP11B2 mRNA encoding the key enzyme for the biosynthesis of aldosterone was detected in both endothelial cells and smooth muscle cells cultivated from human pulmonary artery. The aldosterone receptor (type 1 mineralocorticoid receptor) gene was also found to be expressed in smooth muscle cells and, to a lesser extent, in endothelial cells. CYP11B2 gene expression in smooth muscle cells was stimulated by angiotensin II, the effector peptide of the renin-angiotensin system. Furthermore, the angiotensin II-induced increase in [3H]leucine incorporation in smooth muscle cells was significantly enhanced by aldosterone but inhibited by ZK 91587, a type 1 mineralocorticoid receptor antagonist. This may indicate that vascular aldosterone participates in the angiotensin II-induced hypertrophy of vascular smooth muscle cells. The present study therefore provides the starting point for a novel understanding of the molecular basis of vascular remodeling and hypertension.
Hatakeyama
H
H
Second Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Miyamori
I
I
Fujita
T
T
Takeda
Y
Y
Takeda
R
R
Yamamoto
H
H
D000450:Aldosterone / Q000096:biosynthesis* / Q000235:genetics; D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000494:pharmacology*; D001483:Base Sequence; D002478:Cells, Cultured; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006984:Hypertrophy; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000804:Angiotensin II; D000450:Aldosterone; D003577:Cytochrome P-450 Enzyme System; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase