Role of protein kinase C in angiotensin II-induced constriction of renal microvessels

Background. Although angiotensin II (Ang II) exerts its action through mult iple vasomotor mechanisms, the contribution of phosphoinositol hydrolysis p roducts to Ang II-induced renal vasoconstriction remains undetermined. Methods. The role of protein kinase C (PKC) in Ang II-induced afferent (AFF ) and efferent (EFF) arteriolar constriction was examined using the isolate d perfused hydronephrotic rat kidney. Results. Ang II (0.3 nmol/L)-induced EFF constriction was refractory to inh ibition of voltage-dependent calcium channels by pranidipine (1 mu mol/L, 1 9 +/- 2% reversal) but was completely reversed by a PKC inhibitor, cheleryt hrine (1 mu mol/L, 96 +/- 2% reversal). Furthermore, direct PKC activation by phorbol myristate acetate (PMA; 1 mu mol/L) caused prominent EFF constri ction, and this constriction was inhibited by manganese and free calcium me dium. In contrast, Ang II-induced AFF constriction was completely abolished by pranidipine (98 +/- 4% reversal) and was partially inhibited by chelery thrine (55 +/- 3% reversal). Although PMA elicited marked AFF constriction, this constriction was insensitive to the calcium antagonist, but was total ly inhibited by manganese or free calcium medium. Conclusions. PKC plays an obligatory role in Ang II-induced EFF constrictio n that requires extracellular calcium entry through nonselective cation cha nnels. In contrast, in concert with our recent findings demonstrating a com plete dilation by thapsigargin, Ang II-induced AFF constriction is mainly m ediated by inositol trisphosphate (IP3) and voltage-dependent calcium chann el pathways, but could not be attributed to the PKC-activated calcium entry pathway (for example, nonselective cation channels). Rather, Ang II-stimul ated PKC may cross-talk to the IP3/voltage-dependent calcium channel pathwa y and could modulate the vasoconstrictor mechanism of the AFF. Thus, the ro le of PKC during Ang II stimulation differs in AFF and EFF, which may const itute segmental heterogeneity in the renal microvasculature.