Author Jesmin S, Sakuma I, Togashi H, Yoshioka M, Hattori Y, Kitabatake A, Miyauchi T.
Title Effects of endothelin receptor antagonist on expression of AT1 and AT2 receptors in the heart of SHR-SP.
Journal J. Cardiovasc. Pharmacol.
Abstract It is already well known that alteration of angiotensin II (Ang II) receptors results in cardiac remodeling in different pathological states, and it is believed that Ang II stimulates the release of endothelin-1 (ET-1). The present study aimed at investigating the interaction between ET-1 and different Ang II receptors in the heart of stroke-prone spontaneously hypertensive rats (SHR-SP). These were treated for 3 months with SB209670, an endothelin-A/endothelin-B dual receptor antagonist, or saline (vehicle) starting from the prehypertensive stage (6 weeks of age). Blood pressure, body weight, heart weight and left ventricular weight were sufficiently decreased after treatment of SHR-SP with SB209670. Ang II type 1 receptor was significantly upregulated in the heart of vehicle-treated SHR-SP compared with the age-matched control, Wistar-Kyoto rat. After endothelin antagonism with SB209670, Ang II type 1 receptor in SHR-SP heart was markedly suppressed. On the other hand, Ang II type 2 receptor was approximately 45% downregulated in the heart of vehicle-treated SHR-SP compared with that of the control, and recovered after endothelin antagonism. The present study demonstrates for the first time the effects of endothelin antagonism on the differential expression and regulation of Ang II receptors in the malignant hypertensive model, SHR-SP, and suggests that the endothelin system may be able to function on the upstream of Ang II signaling.
Volume 44 Suppl 1
Pages S59-63
Published 2004-11
PII 00005344-200411001-00016
PMID 15838360
MeSH Angiotensin II / metabolism Animals Coronary Vessels / drug effects* Coronary Vessels / metabolism Disease Models, Animal Endothelin A Receptor Antagonists* Endothelin B Receptor Antagonists* Endothelin-1 / metabolism Hypertension / complications Hypertension / drug therapy* Hypertension / metabolism Indans / pharmacology* Male Myocardium / metabolism Rats Rats, Inbred SHR Rats, Inbred WKY Receptor, Angiotensin, Type 1 / metabolism* Receptor, Angiotensin, Type 2 / metabolism* Receptor, Endothelin A / metabolism Receptor, Endothelin B / metabolism Signal Transduction / drug effects Stroke / etiology Stroke / metabolism
IF 2.371
Times Cited 0
Rats WKY/Ezo(strainID=568) SHRSP/Ezo(strainID=357)