Role of endothelium on the abnormal Angiotensin-mediated vascular functions in epileptic rats


Epidemiological studies have found that the risk for cardiovascular disease is increased in patients with epilepsy. The Renin Angiontensin System (RAS), an important player in vascular tone control, is also involved in many neurological disorders, including seizures and epilepsy. Although it has been reported that Angiotensin II (Ang II) release and Angiotensin receptors expression are altered in many cerebral areas in patients/animal models with neurological disorders, there are no data on the vascular function. We evaluated Ang I and Ang II-mediated vascular responses and to correlate their contractile responses to the pres- ence of endothelium and the protein levels of components of the RAS (AT1, AT2, Mas and ACE) in aorta isolated from genetically epileptic rats (WAR strain). The major finding was that the vascular contractile response induced by Ang I and Ang II is endothelium-dependent. Ang II induced contractions in aortas from Wistar rats either with intact endothelium (E+) (1.16 ± 0.04 g, n = 6) and endothelium-denuded (E-) (1.24 ± 0.04 g, n = 6). Maximum contractile response (ME) induced by Ang I was lower in Wistar E+ (0.45 ± 0.03 g, n = 6) compared with Wistar E- (1.13 ± 0.08 g, n = 6). Ang I and Ang II failed to induce contraction in WAR E+, whereas the ME induced by Ang I in WAR E- was lower (0.52 ± 0.04 g, n = 11) than in the Wistar. ME induced by Ang II in aortas from WAR was also lower (0.40 ± 0.03 g, n = 11) compared with Wistar. AT1 receptor expression in both E+ WAR and Wistar was lower than in both E- WAR and Wistar. AT2 and Mas receptor expression was higher in Wistar E- and E+ as compared to WAR E- and E+. ACE expression was higher in both E+ WAR and Wistar, but it was lower in both E- WAR and Wistar. Endothelium impairs the contractile response induced by Angiotensin in WAR, suggesting that endothelial relaxing factors play important role on the aorta contraction.

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Restini, C. , Reis, R. , Costa-Neto, C. , Garcia-Cairasco, N. , Cortes-de-Oliveira, J. and Bendhack, L. (2012) Role of endothelium on the abnormal Angiotensin-mediated vascular functions in epileptic rats. Journal of Biophysical Chemistry, 3, 174-182. doi: 10.4236/jbpc.2012.32019.

Conflicts of Interest

The authors declare no conflicts of interest.


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