Fauaz Grasiele, Feres Teresa, Farias Nelson C, Paiva Antonio C M, Paiva Therezinha B
Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, Brazil.
Vascul Pharmacol. 2003 Feb;40(2):127-31. doi: 10.1016/s1537-1891(03)00002-8.
Previous works have shown that the alpha(2)-adrenoceptor agonist UK 14,304 induced the relaxation and hyperpolarization of the rat aorta, mediated by alpha(2)-adrenoceptors present in the smooth muscles, through small-conductance, ATP-sensitive K(+) channels. We now report that in spontaneously hypertensive rat (SHR) aortic rings, UK 14,304 induced concentration-dependent hyperpolarizing responses, which were inhibited by yohimbine, an alpha(2)-adrenoceptor inhibitor, and by glibenclamide, a specific inhibitor of small-conductance, ATP-sensitive K(+) channels. The responses were also partially inhibited by iberiotoxin and by apamin. Treatment with N(omega)-nitro-L-arginine (L-NNA) did not affect the response to UK 14,304. These results indicate that alpha(2)-adrenoceptors are present in SHR aortic smooth muscle cell membranes, but differ from those of normotensive animals regarding the K(+) channels involved in their responses. Moreover, the resting membrane potential (RMP) was significantly more negative in SHR than in normotensive rats. This relative hyperpolarized state is probably due to Ca(2+)-dependent K(+) channels being constitutively open in SHR, since the addition of iberiotoxin caused a significant depolarization of the aortic smooth muscle membranes in this strain.
先前的研究表明，α₂ - 肾上腺素能受体激动剂UK 14,304可诱导大鼠主动脉舒张和超极化，这是由存在于平滑肌中的α₂ - 肾上腺素能受体介导的，通过小电导、ATP敏感性钾通道实现。我们现在报告，在自发性高血压大鼠（SHR）主动脉环中，UK 14,304可诱导浓度依赖性超极化反应，该反应可被α₂ - 肾上腺素能受体抑制剂育亨宾以及小电导、ATP敏感性钾通道的特异性抑制剂格列本脲所抑制。该反应也被iberiotoxin和蜂毒明肽部分抑制。用N（ω）-硝基-L-精氨酸（L-NNA）处理不影响对UK 14,304的反应。这些结果表明，α₂ - 肾上腺素能受体存在于SHR主动脉平滑肌细胞膜中，但在参与其反应的钾通道方面与正常血压动物不同。此外，SHR的静息膜电位（RMP）比正常血压大鼠明显更负。这种相对超极化状态可能是由于SHR中钙依赖性钾通道持续开放，因为加入iberiotoxin会导致该品系主动脉平滑肌膜显著去极化。
