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

Worku Abebe, K. M. MacLeod

Research output: Contribution to journalArticle

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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 weeks 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 x 10-8 M) caused marked inhibition of contractile responses to a maximum concentration of NA (10-5 M in aortae; 3 x 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 x 10-8 M) caused marked attenuation of contractile responses of arteries from control and diabetic rats to a maximum concentration of PDB (3 x 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 x 10-6 M) or verapamil (3 x 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.

Original languageEnglish (US)
Pages (from-to)465-471
Number of pages7
JournalBritish Journal of Pharmacology
Volume101
Issue number2
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

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Mesenteric Arteries
Protein Kinase C
Phorbol 12,13-Dibutyrate
Arteries
Aorta
Staurosporine
Norepinephrine
Experimental Diabetes Mellitus
Protein C Inhibitor
Protein Kinase Inhibitors
Streptozocin
Verapamil

ASJC Scopus subject areas

  • Pharmacology

Cite this

Protein kinase C-mediated contractile responses of arteries from diabetic rats. / Abebe, Worku; MacLeod, K. M.

In: British Journal of Pharmacology, Vol. 101, No. 2, 01.01.1990, p. 465-471.

Research output: Contribution to journalArticle

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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 weeks 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 x 10-8 M) caused marked inhibition of contractile responses to a maximum concentration of NA (10-5 M in aortae; 3 x 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 x 10-8 M) caused marked attenuation of contractile responses of arteries from control and diabetic rats to a maximum concentration of PDB (3 x 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 x 10-6 M) or verapamil (3 x 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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N2 - 1. The role of protein kinase C (PKC) in mediating enhanced contractile responses of aortae and mesenteric arteries from male rats with 12-14 weeks 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 x 10-8 M) caused marked inhibition of contractile responses to a maximum concentration of NA (10-5 M in aortae; 3 x 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 x 10-8 M) caused marked attenuation of contractile responses of arteries from control and diabetic rats to a maximum concentration of PDB (3 x 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 x 10-6 M) or verapamil (3 x 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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