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  • Title: Alterations in basal protein kinase C activity modulate renal afferent arteriolar myogenic reactivity.
    Author: Kirton CA, Loutzenhiser R.
    Journal: Am J Physiol; 1998 Aug; 275(2):H467-75. PubMed ID: 9683434.
    Abstract:
    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.
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