Conger J D, Falk S A
Department of Medicine, University of Colorado Health Sciences Center, Denver 80220.
Am J Physiol. 1993 Jan;264(1 Pt 2):F134-40. doi: 10.1152/ajprenal.1993.264.1.F134.
Studies in intact renovascular models have shown that calcium entry blockers inhibit angiotensin (ANG II)-induced vasoconstriction in afferent (AA) but not efferent arterioles (EA), suggesting that increases in smooth muscle cell cytosolic calcium, the initiating intracellular message, result from entry through potential-operated channels in AA, but from organelle storage mobilization or entry through nonpotential-operated channels in EA. The present study examined the effects of diltiazem (10(-5) M) on the constrictor responses to KCl (50 mM) and half-maximal constricting concentrations (EC50) of ANG II and the effects of low-calcium bathing medium on EC50 ANG II responses in isolated rat AA and EA. KCl caused slightly greater decreases in lumen diameter in AA than in EA (P < 0.05) that were completely inhibited by diltiazem in both. Vasoconstriction to ANG II was significantly inhibited by diltiazem (29 +/- 12 vs. 67 +/- 31%; P < 0.02) in AA. However, constrictor response to ANG II in EA was unchanged by diltiazem (42 +/- 32 vs. 41 +/- 31%). Constriction to ANG II of AA in low-calcium medium was significantly attenuated (8 +/- 13 vs. 54 +/- 12%; P < 0.01); however, EA constrictor response was not affected (43 +/- 22 vs. 51 +/- 19%). These data indicate that EC50 ANG II-induced AA constriction requires calcium entry primarily through potential-operated channels. While potential-operated calcium entry channels can be functionally expressed in EA, intracellular calcium mobilization is the primary mechanism for ANG II-induced constriction.
在完整的肾血管模型中的研究表明，钙通道阻滞剂抑制血管紧张素（ANG II）诱导的传入小动脉（AA）而非出球小动脉（EA）的血管收缩，这表明平滑肌细胞胞质钙的增加作为起始的细胞内信号，在AA中是通过电压门控通道进入导致的，而在EA中是通过细胞器钙库释放或通过非电压门控通道进入导致的。本研究检测了地尔硫䓬（10⁻⁵ M）对氯化钾（50 mM）收缩反应以及对ANG II半数最大收缩浓度（EC50）的影响，以及低钙浴液对分离的大鼠AA和EA中ANG II的EC50反应的影响。氯化钾导致AA管腔直径的减小略大于EA（P < 0.05），二者均被地尔硫䓬完全抑制。地尔硫䓬显著抑制了AA中对ANG II的血管收缩（29 ± 12% 对 67 ± 31%；P < 0.02）。然而，地尔硫䓬对EA中ANG II的收缩反应无影响（42 ± 32% 对 41 ± 31%）。在低钙培养基中，AA对ANG II的收缩显著减弱（8 ± 13% 对 54 ± 12%；P < 0.01）；然而，EA的收缩反应未受影响（43 ± 22% 对 51 ± 19%）。这些数据表明，EC50的ANG II诱导的AA收缩主要需要通过电压门控通道进入钙。虽然电压门控钙通道在EA中可功能性表达，但细胞内钙动员是ANG II诱导收缩的主要机制。
