Aldosterone biosynthesis and action in vascular cells.
In view of the hypothetical possibility that the vascular renin-angiotensin system (RAS) might include aldosterone biosynthesis and action in the vasculature, we have undertaken a study to identify aldosterone released into the perfusion circuit from the rat mesenteric artery, and to investigate the effects of an angiotensin converting enzyme inhibition (ACEI) on aldosterone production from the vasculature. After 30 min equilibration, 240 mL of perfusate was collected and subjected to reverse-phase HPLC and subsequent mass spectrometry. Mass spectra corresponding to authentic corticosterone and aldosterone were obtained from the samples of mesenteric artery perfusate. Production of aldosterone in the mesenteric artery was not changed by adrenalectomy, although it was reduced in the arterial perfusate from rats pretreated with ACEI. By RT-PCR the expression of CYP 11B2 and mineralocorticoid receptor genes were demonstrated in both vascular endothelial and smooth muscle cells. These studies constitute indirect evidence supporting our hypothesis that locally produced aldosterone in the vascular tissue acts on vascular tone and remodeling via a paracrine or autocrine manner.
Takeda
R
R
Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Hatakeyama
H
H
Takeda
Y
Y
Iki
K
K
Miyamori
I
I
Sheng
W P
WP
Yamamoto
H
H
Blair
I A
IA
D000450:Aldosterone / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010477:Perfusion; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D013252:Steroid 11-beta-Hydroxylase / Q000096:biosynthesis*; D013256:Steroids / Q000378:metabolism*
D018161:Receptors, Mineralocorticoid; D013256:Steroids; D000450:Aldosterone; D003577:Cytochrome P-450 Enzyme System; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase