ALTERATIONS IN BASAL PROTEIN-KINASE-C ACTIVITY MODULATE RENAL AFFERENT ARTERIOLAR MYOGENIC REACTIVITY

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 afferen t arteriole to pressure and the efficiency of PGC control are subject to physiological and pathophysiological alterations, but the determina nts of the myogenic response of this vessel are largely unknown. We us ed the in vitro perfused hydronephrotic rat kidney to investigate the role of protein kinase C (PKC) in the control of this response. Inhibi tion of PKC by 1 mu M 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 end othelin-1 (3 pM) potentiated myogenic vasoconstriction without affecti ng basal afferent arteriolar diameters. These actions were blocked by 1 mu M chelerythrine, suggesting a PKC-dependent mechanism. Finally, a lthough PKC inhibition attenuated basal myogenic responses, full react ivity to pressure was restored by 1 mM 4-aminopyridine, a pharmacologi cal inhibitor of delayed rectifier K channels, which are known to be m odulated by PKC. The ability of 4-aminopyridine to circumvent the effe cts of PKC inhibition militates against a direct role of PKC in myogen ic signaling. We interpret these observations as indicating that basal PKC activity is an important determinant of myogenic reactivity in th e renal afferent arteriole. However, PKC activation does not appear to play an obligate role in myogenic signaling in this vessel. We sugges t that basal PKC activity directly modulates voltage-gated K channel a ctivity, thereby indirectly affecting myogenic reactivity.