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.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Jesmin S,Sakuma I,Togashi H,Yoshioka M,Hattori Y,Kitabatake A,Miyauchi Tdoi
10.1097/01.fjc.0000166223.57970.5fsubject
Has Abstractpub_date
2004-11-01 00:00:00pages
S59-63eissn
0160-2446issn
1533-4023pii
00005344-200411001-00016journal_volume
44 Suppl 1pub_type
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