Article ; Online: Activation of Coronary Arteriolar PKCβ2 Impairs Endothelial NO-Mediated Vasodilation: Role of JNK/Rho Kinase Signaling and Xanthine Oxidase Activation.
International journal of molecular sciences
2021 Volume 22, Issue 18
Abstract: Protein kinase C (PKC) activation can evoke vasoconstriction and contribute to coronary disease. However, it is unclear whether PKC activation, without activating the contractile machinery, can lead to coronary arteriolar dysfunction. The ... ...
| Abstract | Protein kinase C (PKC) activation can evoke vasoconstriction and contribute to coronary disease. However, it is unclear whether PKC activation, without activating the contractile machinery, can lead to coronary arteriolar dysfunction. The vasoconstriction induced by the PKC activator phorbol 12,13-dibutyrate (PDBu) was examined in isolated porcine coronary arterioles. The PDBu-evoked vasoconstriction was sensitive to a broad-spectrum PKC inhibitor but not affected by inhibiting PKCβ2 or Rho kinase. After exposure of the vessels to a sub-vasomotor concentration of PDBu (1 nmol/L, 60 min), the endothelium-dependent nitric oxide (NO)-mediated dilations in response to serotonin and adenosine were compromised but the dilation induced by the NO donor sodium nitroprusside was unaltered. PDBu elevated superoxide production, which was blocked by the superoxide scavenger Tempol. The impaired NO-mediated vasodilations were reversed by Tempol or inhibition of PKCβ2, xanthine oxidase, c-Jun N-terminal kinase (JNK) and Rho kinase but were not affected by a hydrogen peroxide scavenger or inhibitors of NAD(P)H oxidase and p38 kinase. The PKCβ2 protein was detected in the arteriolar wall and co-localized with endothelial NO synthase. In conclusion, activation of PKCβ2 appears to compromise NO-mediated vasodilation via Rho kinase-mediated JNK signaling and superoxide production from xanthine oxidase, independent of the activation of the smooth muscle contractile machinery. |
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| MeSH term(s) | Animals ; Coronary Vessels/metabolism ; Endothelium, Vascular/metabolism ; Immunohistochemistry ; NADPH Oxidases/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Phorbol 12,13-Dibutyrate/pharmacology ; Protein Kinase C beta/genetics ; Protein Kinase C beta/metabolism ; Reactive Oxygen Species/metabolism ; Superoxides/metabolism ; Swine ; Vasodilation/genetics ; Vasodilator Agents/pharmacology ; Xanthine Oxidase/metabolism |
| Chemical Substances | Reactive Oxygen Species ; Vasodilator Agents ; Superoxides (11062-77-4) ; Nitric Oxide (31C4KY9ESH) ; Phorbol 12,13-Dibutyrate (37558-16-0) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Xanthine Oxidase (EC 1.17.3.2) ; NADPH Oxidases (EC 1.6.3.-) ; Protein Kinase C beta (EC 2.7.11.13) |
| Language | English |
| Publishing date | 2021-09-09 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 2019364-6 |
| ISSN | 1422-0067 ; 1422-0067 ; 1661-6596 |
| ISSN (online) | 1422-0067 |
| ISSN | 1422-0067 ; 1661-6596 |
| DOI | 10.3390/ijms22189763 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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