ラット頸動脈におけるプロテインキナーゼC活性化薬誘導性収縮反応はプロテインキナーゼCβを介して誘導される

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Background: Protein kinase C (PKC)β has been reported to be activated in the vasculature in diabetes and contributes to the microvascular and macrovascular complications by causing inflammation. On the other hand, PKC is also a regulator of smooth muscle contraction, thus possibly alteration of PKCβ activity may affect vascular homeostasis, resulting in contributing the complications. 

Purposes: In this study, we examined role of PKCβ in vascular contractile response in the vascular site.

Methods and Results: We employed male PKCβ knockout (KO) rats and measure vascular contraction in response to PKC activator, phorbol 12-myristate 13-acetate (PMA). Treatment of thoracic aorta with PMA induced contraction, but there was no difference between genotypes (n=5-6). Treatment of carotid artery with PMA induced contraction, which was strongly abolished by PKCβ deficiency (n=6-7, p<0.05). Treatment of femoral arteries with PMA slightly induce contraction, but there was no difference between genotypes (n=4-5). In carotid arteries of male Wistar rats, pretreatment with LY333531, a PKCβ inhibitor (1 μM, 30 min) significantly decreased the contractile response to PMA (n=4, p<0.05). PKCβ mRNA levels in carotid artery were not significantly increased compared with aorta or femoral artery (n=4-6).

Conclusions: PKCβ is strongly associated with PMA-induced contraction in rat carotid artery, suggesting that PKCβ activation may enhance the contractile response in carotid arteries during conditions that involve PKCβ activation including hyperglycemia.