AT(1) angiotensin II receptor and novel non-AT(1), non-AT(2) angiotensin II/III binding site in brainstem cardiovascular regulatory centers of the spontaneously hypertensive rat

Biological Sciences, Northwest Missouri State University, Maryville, MO 64468, USA.
Brain research (Impact Factor: 2.84). 11/2010; 1359:98-106. DOI: 10.1016/j.brainres.2010.08.081
Source: PubMed


Spontaneously hypertensive rats (SHR) have an activated brain angiotensin system that contributes to the elevation of blood pressure in this animal model. Physiological and pharmacological studies suggest that hyperactivation of brain AT₁ angiotensin receptors is a major pathophysiological factor. Consistent with these observations, radioligand binding studies indicate widespread up-regulation of brain angiotensin receptors in SHR. One key brainstem site in which AT₁ receptor stimulation appears to contribute to the elevated blood pressure in SHR is the rostral ventrolateral medulla (RVLM). However, no quantitative comparison of AT₁ receptor binding in the RVLM has been made in SHR versus normotensive rats. A novel, non-AT₁, non-AT₂ binding site, specific for angiotensins II and III, has recently been discovered in the brain. To determine if radioligand binding to either AT₁ receptors or this novel angiotensin binding site is altered in the RVLM and other caudal brainstem regions of SHR, a quantitative densitometric autoradiographic comparison of radioligand binding in SHR versus normotensive Wistar-Kyoto rats was made. In both the RVLM and caudal ventrolateral medulla (CVLM) as well as dorsomedial medulla (DMM), there was increased expression of AT₁ receptor binding in SHR (13%, 9%, and 23%, respectively). Conversely, expression of the novel, non-AT₁, non-AT₂, angiotensin II and III binding site was decreased in the RVLM and DMM of SHR (37% and 13%, respectively). This increased AT₁ receptor binding in the RVLM may contribute to the hypertension of SHR. Reduced radioligand binding to the novel, non-AT₁, non-AT₂, angiotensin binding site in the RVLM of SHR may indicate a role for this binding site to reduce blood pressure via its interactions with angiotensins II and III.

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    • "Bourassa et al. [45] demonstrated that AT1 receptor binding in both RVLM and caudal ventrolateral medulla as well as dorsomedial medulla was increased in SHR compared with normotensive rats. Conversely, expression of the novel, non-AT1, non-AT2, Ang II and III binding site, which was recently discovered, might be decreased in the RVLM and dorsomedial medulla of SHR [45]. "
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