Kirton C A, Loutzenhiser R
Smooth Muscle Research Group, Department of Pharmacology and Therapeutics, The University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Am J Physiol. 1998 Aug;275(2):H467-75. doi: 10.1152/ajpheart.1998.275.2.H467.
Myogenic vasoconstriction of the renal afferent arteriole contributes to the autoregulation of renal blood flow, glomerular filtration rate, and glomerular capillary pressure (PGC). The reactivity of the afferent arteriole to pressure and the efficiency of PGC control are subject to physiological and pathophysiological alterations, but the determinants of the myogenic response of this vessel are largely unknown. We used the in vitro perfused hydronephrotic rat kidney to investigate the role of protein kinase C (PKC) in the control of this response. Inhibition of PKC by 1 microM chelerythrine attenuated myogenic reactivity but did not affect the afferent arteriole vasoconstrictor response to KCl (35 mM)-induced depolarization. Low concentrations of phorbol ester (10 nM phorbol 12-myristate 13-acetate) and low levels of ANG II or endothelin-1 (3 pM) potentiated myogenic vasoconstriction without affecting basal afferent arteriolar diameters. These actions were blocked by 1 microM chelerythrine, suggesting a PKC-dependent mechanism. Finally, although PKC inhibition attenuated basal myogenic responses, full reactivity to pressure was restored by 1 mM 4-aminopyridine, a pharmacological inhibitor of delayed rectifier K channels, which are known to be modulated by PKC. The ability of 4-aminopyridine to circumvent the effects of PKC inhibition militates against a direct role of PKC in myogenic signaling. We interpret these observations as indicating that basal PKC activity is an important determinant of myogenic reactivity in the renal afferent arteriole. However, PKC activation does not appear to play an obligate role in myogenic signaling in this vessel. We suggest that basal PKC activity directly modulates voltage-gated K channel activity, thereby indirectly affecting myogenic reactivity.
肾入球小动脉的肌源性血管收缩有助于肾血流量、肾小球滤过率和肾小球毛细血管压力（PGC）的自身调节。入球小动脉对压力的反应性以及PGC控制的效率会受到生理和病理生理改变的影响，但该血管肌源性反应的决定因素在很大程度上尚不清楚。我们使用体外灌注的肾积水大鼠肾脏来研究蛋白激酶C（PKC）在控制这种反应中的作用。用1 microM白屈菜红碱抑制PKC可减弱肌源性反应性，但不影响入球小动脉对KCl（35 mM）诱导的去极化的血管收缩反应。低浓度的佛波酯（10 nM佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯）以及低水平的血管紧张素II或内皮素 - 1（3 pM）可增强肌源性血管收缩，而不影响基础入球小动脉直径。这些作用被1 microM白屈菜红碱阻断，提示存在PKC依赖性机制。最后，虽然PKC抑制减弱了基础肌源性反应，但1 mM 4 - 氨基吡啶可恢复对压力的完全反应性，4 - 氨基吡啶是一种已知受PKC调节的延迟整流钾通道的药理学抑制剂。4 - 氨基吡啶规避PKC抑制作用的能力表明PKC在肌源性信号传导中不发挥直接作用。我们将这些观察结果解释为表明基础PKC活性是肾入球小动脉肌源性反应性的重要决定因素。然而，PKC激活在该血管的肌源性信号传导中似乎并非起必不可少的作用。我们认为基础PKC活性直接调节电压门控钾通道活性，从而间接影响肌源性反应性。
