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Publication : Protein kinase Cα deletion causes hypotension and decreased vascular contractility.

First Author  Wynne BM Year  2018
Journal  J Hypertens Volume  36
Issue  3 Pages  510-519
PubMed ID  29120956 Mgi Jnum  J:280032
Mgi Id  MGI:6367517 Doi  10.1097/HJH.0000000000001596
Citation  Wynne BM, et al. (2018) Protein kinase Calpha deletion causes hypotension and decreased vascular contractility. J Hypertens 36(3):510-519
abstractText  AIM: Protein kinase Calpha (PKCalpha) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCalpha causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCalpha has been shown to modulate nephron ion transport. However, the role of PKCalpha in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCalpha knock out (PKC KO) to test the hypothesis that global PKCalpha deficiency would reduce MAP, by a reduction in vascular contractility. METHODS: Radiotelemetry measurements of ambulatory blood pressure (day/night) were obtained for 18 h/day during both normal chow and high-salt (4%) diet feedings. PKCalpha mice had a reduced MAP, as compared with control, which was not normalized with high-salt diet (14 days). Metabolic cage studies were performed to determine urinary sodium excretion. RESULTS: PKC KO mice had a significantly lower diastolic, systolic and MAP as compared with control. No significant differences in urinary sodium excretion were observed between the PKC KO and control mice, whether fed normal chow or high-salt diet. Western blot analysis showed a compensatory increase in renal sodium chloride cotransporter expression. Both aorta and mesenteric vessels were removed for vascular reactivity studies. Aorta and mesenteric arteries from PKC KO mice had a reduced receptor-independent relaxation response, as compared with vessels from control. Vessels from PKC KO mice exhibited a decrease in maximal contraction, compared with controls. CONCLUSION: Together, these data suggest that global deletion of PKCalpha results in reduced MAP due to decreased vascular contractility.
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