Journal article
Angiotensin II- and IV-induced changes in cerebral blood flow. Roles of AT1, AT2, and AT4 receptor subtypes
Regulatory peptides, Vol.68(2), pp.131-138
01/29/1997
Handle:
https://hdl.handle.net/2376/109575
PMID: 9110385
Abstract
Our laboratory has previously reported the discovery of a unique angiotensin binding site (termed AT4) specific for angiotensin IV (AngIV) in cultured vascular endothelial and smooth muscle cells. The present investigation employed laser-Doppler flowmetry to examine the effect of angiotensin II (AngII) and AngIV stimulation of these receptors on cerebral microcirculation in anesthetized Sprague-Dawley rats. Internal carotid artery infusion of AngII at a low dose (0.1 pmol min-1) revealed a 23% reduction in cerebral blood flow (CBF), while the infusion of AngIV increased CBF in a dose-dependent fashion with the highest dose (100 pmol min-1) resulting in an elevation of 30%. In a second experiment separate groups of rats were pre-treated with the AT1 receptor subtype antagonist DuP 753 (Losartan), the AT2 receptor subtype antagonist PD123177, or a newly synthesized AT4 receptor subtype antagonist Divalinal-AngIV (Divalinal), followed by AngII or AngIV for the purpose of determining which angiotensin receptor subtype is responsible for mediating these AngII- and AngIV-induced responses. Pre-treatment with Losartan completely blocked subsequent AngII-induced reductions in CBF, while both PD123177 and Divalinal failed to inhibit this response. In contrast, significant increases in CBF were measured due to AngIV stimulation following pre-treatment with Losartan and PD 123177, while Divalinal abolished this AngIV-induced response. These results suggest that AngII and IV play opposite roles in cerebral microcirculation, i.e., the AT1 receptor subtype mediates AngII-induced reductions in CBF, while the AT4 receptor subtype regulates increases in CBF.
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Details
- Title
- Angiotensin II- and IV-induced changes in cerebral blood flow. Roles of AT1, AT2, and AT4 receptor subtypes
- Creators
- E A Kramár - Department of Psychology, Washington State University, Pullman 99164-4820, USAJ W HardingJ W Wright
- Publication Details
- Regulatory peptides, Vol.68(2), pp.131-138
- Academic Unit
- Psychology, Department of; Integrative Physiology and Neuroscience, Department of
- Publisher
- Netherlands
- Identifiers
- 99900547048401842
- Language
- English
- Resource Type
- Journal article