Effect of protein kinase C and protein kinase A inhibitors on contraction of isolated femoral arteries of SHR and Wistar rats

Author:

Bal MS,Paulis L,Zicha J,Kuneš J

Abstract

Alterations of calcium handling and other second messenger cascades including protein kinase C (PKC) and A (PKA) were suggested to be responsible for abnormal vascular function in spontaneously hypertensive rats (SHR). However, the relative contribution of these pathways to vasoconstriction is still not completely understood. We investigated the effect of Ro 31-8220 (PKC inhibitor) and H89 (PKA inhibitor) on vasoconstriction induced by 120 mM KCl or by addition of 10 µM noradrenaline (NA) in isolated femoral arteries of control Wistar rats and SHR. Moreover, we investigated these responses in the presence and absence of Ca2+ ions in the incubation medium in order to assess the role of calcium influx in these contractions. We observed that while the vasoconstriction in the presence of calcium was not different between Wistar and SHR, the difference between constriction elicited by NA addition in the absence and presence of external calcium was larger in SHR. The inhibition of PKC had no effect on constrictions in SHR, but diminished constrictions in Wistar rats. PKA inhibition slightly enhanced constrictions in Wistar rats, but reduced them in the presence of calcium in SHR. We conclude that vasoconstriction elicited by adrenergic stimulation is more dependent on extracellular calcium influx in SHR compared to Wistar rats. Moreover, the activation of PKA contributes to this calcium-dependent vasoconstriction in SHR but not in Wistar. On the other hand, PKC activation seems to play a less important role in vasoconstriction in SHR than in Wistar rats.

Publisher

Institute of Physiology of the Czech Academy of Sciences

Subject

General Medicine,Physiology

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