MORIMOTO Satoshi    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Associate Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Central effects of endothelin and its antagonists on sympathetic and cardiovascular regulation in SHR-SP.
Journal	Formal name：Journal of cardiovascular pharmacology Abbreviation：J Cardiovasc Pharmacol ISSN code：01602446/01602446
Domestic / Foregin	Foregin
Volume, Issue, Page	33(6),pp.876-82
Author and coauthor	Nakamura K, Sasaki S, Moriguchi J, Morimoto S, Miki S, Kawa T, Itoh H, Nakata T, Takeda K, Nakagawa M
Publication date	1999/06
Summary	Intracerebroventricular injections of endothelin-1 (ET-1) are reported to cause dose-related increases in sympathetic nerve activity and blood pressure in anesthetized normotensive rats. These studies were performed to determine the following: which endothelin receptor, A or B, is involved in mediating sympathetic and cardiovascular effects of ET-1 injected centrally; whether central endothelin tonically participates in blood pressure regulation in normotensive rats; and whether the altered endothelin system in the central nervous system contributes to blood pressure elevation in hypertensive rats. ET-1, ET-A antagonist (BQ-123), or ET-B antagonist (RES-701-1) was injected into the lateral cerebral ventricle (i.c.v.) of urethane-anesthetized normotensive Wistar and Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHRs), and stroke-prone SHRs (SHR-SPs). In Wistar rats, i.c.v. injections of ET-1 (1, 5, 10 pmol) consistently increased sympathetic nerve activity, thereby elevating blood pressure in a dose-related manner. The pressor responses induced by i.c.v. ET-1 were abolished after intravenous pretreatment with phentolamine. Neither ET-A nor ET-B antagonist, when injected centrally, altered basal levels of sympathetic nerve activity, heart rate, or blood pressure in Wistar rats. However, sympathetic activation and pressor responses induced by i.c.v. injection of endothelin were completely abolished after i.c.v. pretreatment with ET-A antagonist but were unaffected after pretreatment with ET-B antagonist. Although i.c.v. injections of ET-1 increased sympathetic nerve activity and blood pressure in WKY rats, SHRs, and SHR-SPs, the magnitudes of these responses did not differ among these three groups. In contrast, i.c.v. injections of ET-A antagonist decreased sympathetic nerve activity, blood pressure, and heart rate only in SHR-SPs, but not in WKY rats and SHRs. In addition, the depressor effects of i.c.v. ET-A antagonist in SHR-SPs were ascertained while th
DOI	10.1097/00005344-199906000-00007
PMID	10367590