1992 Fiscal Year Final Research Report Summary
Analysis of effect of endothelin on blood pressure and its physiological meanings
| Project/Area Number |
02304033
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | KYOTO UNIVERSITY (1991-1992)
University of Tsukuba (1990) |
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Principal Investigator |
MASAKI Tomoh Kyoto Univ. Dep.Pharmacol. Prof., 医学部, 教授 (60009991)
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| Co-Investigator(Kenkyū-buntansha) |
YAZAKI Yoshio Univ. Tokyo Dep.of Med. Prof., 医学部, 教授 (20101090)
TODA Noboru Shiga Univ. of Med. Sci. Dep. of Med. Prof., 医学部, 教授 (50025590)
HIRATA Yasunobu Univ. Tokyo Dep. of Cardiology,Res.Associ., 医学部, 助手 (70167609)
TAIRA Norio Tohoku Univ. Dep. Pharmacol Prof., 医学部, 教授 (60004553)
GOTO Katsutoshi Univ. Tsukuba, Inst. Basic Med. Sci. Prof., 基礎医学系, 教授 (30012660)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Blood pressure / Endothelin / Vasodilation / Vasoconstriction |
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| Research Abstract |
Endothelin is a potent vasoconstrictor peptide produced by endothelial cells. Intravenous injection of a bolus of endothelin elicited an initial transient depressor response followed by a long-lasting pressor response. The pressor response was partly abolished by a calcium antagonist and ascribed to vasoconstriction of peripheral reistant vascular beds. However, an increasing amount of experimental results demonstrated that the blood pressure in response to endothelin varies depending upon the vascular beds employed. To elucidate the complexity and the physiological significance of endothelin, we have studied endothelin actions on systemic blood pressure from various standpoints. Along with our experimental results, an increasing amount of papers on endothelin-induced pressor responses revealed that endothelin may play some role in maintenance of blood pressure as a local hormone but not as a circulating hormone. Endothelin may be produced by endothelial cells by unknown factors in blo
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od stream and released to the basal side of the endothelium and act on the underlying smooth muscle cells. Plasma level of endothelin does not change even when the concentration of endothelin in intima increases remarkably, suggesting a role of endothelin in regulation of vascular tonus. ETA, a subtype of endothelin receptors exists on vascular smooth muscle and mediates vasoconstriction. Another subtype of endothelin receptor, ETB, exists on endothelial cells and mediates vasodilation via releasing endothelium-derived relaxing factor. However, recent experimental results demon- strate that ETB exists also in some vascular beds and mediate vasoconstriction. The diverse distribution of ETA and ETB receptors in endothelial cells and smooth muscle cells in various vascular beds produces a diversity of responses of systemic blood pressure in various species and vascular beds to endothelin. Additionally, endothelin-induced vasoconstriction was interfered by other vasoactive substances such as serotonine, suggesting more diverse response of blood pressure to endothelin. Less
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