Noradrenaline released from sympathetic nerves by activating alpha₁-adrenergic receptors causes renal artery contraction, in particular, through an inhibition of the myosin light chain phosphatase by Rho kinase (RhoK) and/or protein kinase C (PKC). In addition, both these kinases are expressed in endothelium and may influence the contraction through inhibition of endothelial NO-synthase (eNOS). The role of these kinases in contraction of renal arteries is poorly understood. Therefore, the goal of our study was to estimate the participation of RhoK and PKC in alpha₁-adrenergic contraction of rat renal arteries and in regulation of eNOS activity.

Interlobar arteries (2–3-order branches of the renal artery) were dissected from the kidney of male Wistar rats and mounted in a wire myograph (DMT A/S, Denmark). The arteries were contracted for 10 min with methoxamine (alpha₁-adrenoceptor agonist, 0.8–1.6 microM) up to 70–80% of the maximal response level. Preincubation with the RhoK inhibitor (Y27632, 3 microM) or PKC inhibitor (GF109203X, 1 microM) decreased the contractile response by 60–70%. However, in the presence of eNOS inhibitor L-NNA (100 microM) Y27632 or GF109203X reduced the contractile response to methoxamine by only 40–50%. Therefore, NOS inhibition attenuated the effects of RhoK and PKC inhibitors.

In conclusion, RhoK and PKC with almost equal potency strongly potentiate smooth muscle contraction in rat renal small arteries. Along with that, vasocontractile effects of these kinases in rat kidney are due to inhibition of endothelial NOS. Supported by RFBR (grant N10-04-01723-a).