Protein kinase C‐mediated contractile responses of arteries from diabetic rats

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Abstract
1 The role of protein kinase C (PKC) in mediating enhanced contractile responses of aortae and mesenteric arteries from male rats with 12–14 week streptozotocin-induced diabetes to noradrenaline (NA) was investigated using the PKC activator, phorbol 12,13-dibutyrate (PDB), and the PKC inhibitor, staurosporine. 2 Maximum contractile responses of aortae and mesenteric arteries from diabetic rats to NA were significantly enhanced compared with responses of arteries from age-matched control animals. The maximum NA responses were increased by 59.6 ± 7.9% in aortae and by 54.9 ± 7.4% in mesenteric arteries from diabetic animals, compared to their respective controls. 3 Pretreatment of aortae and mesenteric arteries from both control and diabetic animals with staurosporine (5 × 10−8 m) caused marked inhibition of contractile responses to a maximum concentration of NA (10−5 m in aortae; 3 × 10−5 m in mesenteric arteries). In the presence of staurosporine, no difference was observed in the magnitude of contractile responses of arteries from control and diabetic rats to NA. 4 Maximum contractile responses of mesenteric arteries from diabetic rats to PDB were significantly increased (by 45.0 ± 4.9%) compared to responses of arteries from control animals. In contrast, no significant difference was found in the magnitude of contractile responses of aortae from control and diabetic rats to PDB. 5 Staurosporine (5 × 10−8 m) caused marked attenuation of contractile responses of arteries from control and diabetic rats to a maximum concentration of PDB (3 × 10−6 m). In the presence of staurosporine, the difference in magnitude of contractile responses of mesenteric arteries from control and diabetic rats to PDB was abolished. 6 Contractile responses of aortae and mesenteric arteries from control and diabetic rats to PDB were reduced in the absence of extracellular Ca2+, and in the presence of the Ca2+ channel blockers, nifedipine (3 × 10−6 m) or verapamil (3 × 10−6 m). Under these conditions, no difference was found in the magnitude of contractile responses of mesenteric arteries from control and diabetic rats to PDB. 7 These data suggest that enhanced contractile responses of aortae and mesenteric arteries from streptozotocin-induced diabetic rats to NA may result, at least in part, from increased activation of PKC. In addition, increased activation of PKC-mediated processes, which are dependent on the presence of extracellular Ca2+, may further contribute to the enhanced contractile responses of diabetic mesenteric arteries to NA.

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