Nagahama T, Hayashi K, Ozawa Y, Takenaka T, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Kidney Int. 2000 Jan;57(1):215-23. doi: 10.1046/j.1523-1755.2000.00822.x.
Role of protein kinase C in angiotensin II-induced constriction of renal microvessels.
Although angiotensin II (Ang II) exerts its action through multiple vasomotor mechanisms, the contribution of phosphoinositol hydrolysis products to Ang II-induced renal vasoconstriction remains undetermined.
The role of protein kinase C (PKC) in Ang II-induced afferent (AFF) and efferent (EFF) arteriolar constriction was examined using the isolated perfused hydronephrotic rat kidney.
Ang II (0.3 nmol/L)-induced EFF constriction was refractory to inhibition of voltage-dependent calcium channels by pranidipine (1 micromol/L, 19 +/- 2% reversal) but was completely reversed by a PKC inhibitor, chelerythrine (1 micromol/L, 96 +/- 2% reversal). Furthermore, direct PKC activation by phorbol myristate acetate (PMA; 1 micromol/L) caused prominent EFF constriction, and this constriction was inhibited by manganese and free calcium medium. In contrast, Ang II-induced AFF constriction was completely abolished by pranidipine (98 +/- 4% reversal) and was partially inhibited by chelerythrine (55 +/- 3% reversal). Although PMA elicited marked AFF constriction, this constriction was insensitive to the calcium antagonist, but was totally inhibited by manganese or free calcium medium.
PKC plays an obligatory role in Ang II-induced EFF constriction that requires extracellular calcium entry through nonselective cation channels. In contrast, in concert with our recent findings demonstrating a complete dilation by thapsigargin, Ang II-induced AFF constriction is mainly mediated by inositol trisphosphate (IP3) and voltage-dependent calcium channel pathways, but could not be attributed to the PKC-activated calcium entry pathway (for example, nonselective cation channels). Rather, Ang II-stimulated PKC may cross-talk to the IP3/voltage-dependent calcium channel pathway and could modulate the vasoconstrictor mechanism of the AFF. Thus, the role of PKC during Ang II stimulation differs in AFF and EFF, which may constitute segmental heterogeneity in the renal microvasculature.
蛋白激酶C在血管紧张素II诱导的肾微血管收缩中的作用
尽管血管紧张素II（Ang II）通过多种血管运动机制发挥作用，但磷酸肌醇水解产物对Ang II诱导的肾血管收缩的作用仍未确定。
使用离体灌注的肾积水大鼠肾脏研究蛋白激酶C（PKC）在Ang II诱导的入球（AFF）和出球（EFF）小动脉收缩中的作用。
血管紧张素II（0.3 nmol/L）诱导的EFF收缩对普拉地平（1 μmol/L）抑制电压依赖性钙通道不敏感（逆转率19±2%），但被PKC抑制剂白屈菜红碱（1 μmol/L）完全逆转（逆转率96±2%）。此外，佛波酯肉豆蔻酸酯（PMA；1 μmol/L）直接激活PKC导致显著的EFF收缩，这种收缩被锰和无钙培养基抑制。相比之下，血管紧张素II诱导的AFF收缩被普拉地平完全消除（逆转率98±4%），并被白屈菜红碱部分抑制（逆转率55±3%）。尽管PMA引起明显的AFF收缩，但这种收缩对钙拮抗剂不敏感，但被锰或无钙培养基完全抑制。
PKC在血管紧张素II诱导的EFF收缩中起重要作用，这需要细胞外钙通过非选择性阳离子通道进入。相比之下，与我们最近的发现一致，即毒胡萝卜素可使其完全舒张，血管紧张素II诱导的AFF收缩主要由三磷酸肌醇（IP3）和电压依赖性钙通道途径介导，但不能归因于PKC激活的钙内流途径（例如非选择性阳离子通道）。相反，血管紧张素II刺激的PKC可能与IP3/电压依赖性钙通道途径相互作用，并可能调节AFF的血管收缩机制。因此，PKC在血管紧张素II刺激过程中的作用在AFF和EFF中有所不同，这可能构成肾微血管系统中的节段性异质性。
