Grant-in-Aid for international Scientific Research
|Allocation Type||Single-year Grants|
|Research Institution||Yokohama City University|
SHIONOIRI Hiroshi Yokohama City University School of Medicine, Associate Professor, 医学部, 講師 (20128599)
BRUNNER Hans R. University of Lausanne School of Medicine, Professor, 医学部(スイス連邦), 教授
SAMBHI Mohinder P. University of California at Los Angeles, School of Medicine, Professor, ロスアンゼルス校医学部, 教授
CHOBANIAN Ar ボストン大学, 医学部, 学部長教授
HIMENO Hideo Yokohama City University Hospital, Clinical Instructor, 医学部病院, 診療医
TAKASAKI Izumi Yokohama City University Hospital, Clinical Instructor, 医学部病院, 診療医
HIROSE Shigehisa Tokyo Institute of Technology, Professor, 理学部, 教授 (10134199)
CHOBANIAN Aram V. Boston University School of Medicine, Dean and Professor
SAMBHI Mohun カリフォルニア大学, 医学部(米国), 教授
CHOBAMIAN Ar 米国、ボストン大学, 医学部, 教授
|Project Period (FY)
1989 – 1991
Completed(Fiscal Year 1991)
|Budget Amount *help
¥11,400,000 (Direct Cost : ¥11,400,000)
Fiscal Year 1991 : ¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1990 : ¥4,000,000 (Direct Cost : ¥4,000,000)
Fiscal Year 1989 : ¥4,100,000 (Direct Cost : ¥4,100,000)
|Keywords||Hypertension / Hypertensive vascular complications / Glucose and lipids metabolism / Smoking / Muscle sympathetic nerve activity / Renin-angiotensin-aldosterone system / Primary aldosteronism / Atrial natriuretic peptide receptors / Endothelin receptors / Fibronectin / プロスタグラジン / フィブロネクチン / アンジオテンシン変換酵素 / 高血圧 / 血管障害 / 動脈硬化|
Clinical and basic studies concerning the cardiovascular risk factors and their contribution to hypertensive vascular diseases have been conducted and summarized as follows.
1. Long-term anti-hypertensive treatment and the metabolism of lipid and glucose.
An alpha1-blocker (terazosin), a Ca^<++>-antagonist (felodipin), angiotensin converting enzyme (ACE) inhibitors (captopril, cilazapril, and lisinopril) were administered to hypertensive patients with or without impaired glucose tolerance for more than 6 months. These antihypertensive drugs controlled the blood pressure well without compromising the lipid and glucose metabolism. Chobanian, a coworker of this project, reported that an ACE inhibitor decreased the cellularity of the atherosclerotic subintimal lesion in Watanabe heritable hyperlipidemic rabbits.
2. Smoking and hypertension.
Smoking caused a significantly greater and prolonged increase of blood pressure in normal young males with positive family history of essential hypertensio
n than in those with negative family history, although the increase in plasma catecholamine was similar in both groups.
3. Sympathetic nervous system and hypertension.
Muscle sympathetic nerve activity in response to cold, mental stress, and vasoactive substances was measured in normotensives, borderline hypertensives, and hypertensives. The results suggested that borderline hypertensives and hypertensives have elevated sympathetic nerve activity, and abnormal baroreceptor reflexes in which endogenous angiotensin II may play a role.
4. Renin-angiotensin-aldosterone system and hypertensive vascular complications.
Hypertensive patients with low plasma renin have been believed to be at low risk for hypertensive vascular complications. Contrary to this belief, our studies revealed relatively high prevalence of hypertensive vascular complications in patients with primary aldosteronism whose plasma active and inactive renin concentration and renin mRNA in both kidneys and adrenals were less than detectable limits.
5. Receptors for vasoactive substances.
We have shown immunohistochemically that the receptor for atrial natriuretic peptide (ANP) was present in human adrenal glomerulosa and medulla. Although ANP suppressed the release of aldosterone from normal adrenal glomerulosa, it could not suppress that from aldosterone-producing adenoma. Hirose, a coworker of this project, isolated and characterized the bovine gene encoding the type C ANP receptor and bovine endothelin ET_B receptor.
6. Fibronectin and hypertensive vasculature.
Fibronectin is one of the major components of extracellular matrix of vasculature which could influence the phenotype of vascular cells. Takasaki and Chobanian, coworkers of this project, have shown that fibronectin gene expression is induced in rat aorta of different hypertensive models including deoxycorticosterone-salt (DOCA/salt), angiotensin II infusion, spontaneously hypertensive rats. More interestingly, EIIIA+ fibronectin, which is known to be fetal form of fibronectin, was found to be selectively induced in aorta of DOCA/salt hypertensive rats. Less