De Mello Walmor C
School of Medicine, Medical Sciences Campus, UPR, San Juan, PR 00936-5067, USA.
J Am Soc Hypertens. 2014 Jan;8(1):14-20. doi: 10.1016/j.jash.2013.08.003. Epub 2013 Nov 9.
The influence of angiotensin (Ang) (1-7) on potassium current (Kv) and resting potential of smooth muscle cells isolated from mesenteric artery of Sprague Dawley rats was investigated. Measurements of potassium current were performed using the whole cell configuration of pCLAMP. The results indicated that Ang (1-7) (10(-9) M) increased the potassium current by 120% ± 2.6% (P < .05) and the resting potential of smooth muscle cells by 8 ± 2.8 mV (n = 23; P < .05). Ang II (10(-9) M) administered to the bath reduced the potassium current by 35% ± 3.6% (n = 23; P < .05) and depolarized the arterial myocytes by 7.8 ± 2.1 mV (n = 25; P < .05). The effect of the heptapeptide on potassium current was inhibited by a Mas receptor inhibitor (A779; 10(-8) M) as well as by a protein kinase A (PKA) inhibitor (10(-9) M) dialyzed into the cell. Intracellular dialysis of the catalytic subunit of PKA (5 × 10(-8) M) enhanced the potassium current by 38% ± 3.4% (n = 14; P < .05) but did not abolish the effect of Ang (1-7). On the other hand, Bis-1 (10(-9) M), which is a specific inhibitor of PKC, suppressed the effect of Ang (1-7) on potassium current. In conclusion, Ang (1-7) counteracts the effect of Ang II on potassium current and membrane potential of smooth muscle cells from mesenteric arteries, which are resistance vessels involved in the regulation of peripheral resistance and blood pressure. The activation of the cAMP/PKA cascade is essential for the effect of the heptapeptide. Pathophysiological implications are discussed.
研究了血管紧张素（Ang）（1 - 7）对从Sprague Dawley大鼠肠系膜动脉分离的平滑肌细胞钾电流（Kv）和静息电位的影响。使用pCLAMP的全细胞配置进行钾电流测量。结果表明，Ang（1 - 7）（10⁻⁹ M）使钾电流增加120% ± 2.6%（P < 0.05），平滑肌细胞静息电位增加8 ± 2.8 mV（n = 23；P < 0.05）。浴槽中加入Ang II（10⁻⁹ M）使钾电流降低35% ± 3.6%（n = 23；P < 0.05），并使动脉肌细胞去极化7.8 ± 2.1 mV（n = 25；P < 0.05）。七肽对钾电流的作用被Mas受体抑制剂（A779；10⁻⁸ M）以及透析入细胞的蛋白激酶A（PKA）抑制剂（10⁻⁹ M）所抑制。PKA催化亚基（5 × 10⁻⁸ M）的细胞内透析使钾电流增加38% ± 3.4%（n = 14；P < 0.05），但并未消除Ang（1 - 7）的作用。另一方面，Bis - 1（10⁻⁹ M），一种PKC的特异性抑制剂，抑制了Ang（1 - 7）对钾电流的作用。总之，Ang（1 - 7）抵消了Ang II对肠系膜动脉平滑肌细胞钾电流和膜电位的作用，肠系膜动脉是参与外周阻力和血压调节的阻力血管。cAMP/PKA级联的激活对于七肽的作用至关重要。讨论了病理生理学意义。
