Production of mineralocorticoid and enzyme expression for steroidogenesis in blood vessels as components of the vascular auto-/paracrine system

Abstract

With the recent advance in immunohistochemical and molecular-genetic techniques, all of the components of the renin-angiotensin system (RAS) have been shown to exist in the vascular tissue of various animal species as well as in humans. The author's group previously reported that angiotensin II (AII) was generated in the mesenteric arteries of several experimental rat models. Vascular AII generation appears to be regulated independently of circulating renin levels, as suggested by the expression of tissue-specific angiotensinogen mRNA. In the light of recent reports that aldosterone may be synthesized in the cultured endothelial cells from bovine aorta, and that 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) plays a key role in determining the specificity in mineralocorticoid activity in various mineralocorticoid-responsive tissues, the author wishes to review the studies carried out by colleagues on the production of aldosterone with its precursor steroids and enzyme expression for aldosterone synthesis in the blood vessels as the components of the vascular auto-/paracrine system. The first part of the present paper is summarized as follows: 1) With Northern blotting and RT-PCR of the RNA which was prepared from rat arterial tissue or cultured human arterial smooth muscle cells (SMC), the expression of mineralo- and glucocorticoid receptors was confirmed. 2) The vascular production of aldosterone and corticosterone from the rat mesenteric artery was demonstrated in analyzing the arterial perfusates using a HPLC and GC/MS. Moreover, in this ex vivo experiment, the production of aldosterone in the vasculature was found to be partially controlled by angiotensin II generated locally. 3) It was clearly demonstrated using an RT-PCR method for the first time that aldosterone synthase, cytochrome P450aldo (c 18 or c mo); CYP 11B2 messenger RNA is expressed in the cultured endothelial cells (EC) from human pulmonary artery. From these data, the author would like to propose the concept of a vascular renin-angiotensin-aldosterone system under which paracrinaly produced mineralocorticoid in the vascular EC may easily reach the vascular SMC and in turn act to increase the vascular tone through binding to the receptor there. The second part can be summarized as follows: 1) The expression of 11 beta-HSD in the vasculature was confirmed by bioassay using ex vivo experiment of the isolated rat mesenteric artery perfusion system, immunocytochemical staining methods, in situ hybridization and also by Northern blot analysis.(ABSTRACT TRUNCATED AT 400 WORDS)