Protein kinase Cα deletion causes hypotension and decreased vascular contractility

Brandi M. Wynne, Cameron G. McCarthy, Theodora Szasz, Patrick A. Molina, Arlene B. Chapman, R Clinton Webb, Janet D. Klein, Robert S. Hoover

Research output: Contribution to journalArticle

Abstract

Aim: Protein kinase Cα (PKCα) 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, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCα knock out (PKC KO) to test the hypothesis that global PKCα 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. PKCα 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 PKCα results in reduced MAP due to decreased vascular contractility.

Original languageEnglish (US)
Pages (from-to)510-519
Number of pages10
JournalJournal of hypertension
Volume36
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Hypotension
Protein Kinase C
Arterial Pressure
Blood Vessels
Salts
Diet
Sodium Chloride Symporters
Aorta
Sodium
Protein C Deficiency
Blood Pressure
Mesenteric Arteries
Nephrons
Ion Transport
Vascular Smooth Muscle
Blood Proteins
Phosphotransferases
Western Blotting
Kidney

Keywords

  • blood pressure
  • hypotension
  • protein kinase Cα
  • vascular contractility
  • vascular reactivity

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Wynne, B. M., McCarthy, C. G., Szasz, T., Molina, P. A., Chapman, A. B., Webb, R. C., ... Hoover, R. S. (2018). Protein kinase Cα deletion causes hypotension and decreased vascular contractility. Journal of hypertension, 36(3), 510-519. https://doi.org/10.1097/HJH.0000000000001596

Protein kinase Cα deletion causes hypotension and decreased vascular contractility. / Wynne, Brandi M.; McCarthy, Cameron G.; Szasz, Theodora; Molina, Patrick A.; Chapman, Arlene B.; Webb, R Clinton; Klein, Janet D.; Hoover, Robert S.

In: Journal of hypertension, Vol. 36, No. 3, 01.03.2018, p. 510-519.

Research output: Contribution to journalArticle

Wynne, BM, McCarthy, CG, Szasz, T, Molina, PA, Chapman, AB, Webb, RC, Klein, JD & Hoover, RS 2018, 'Protein kinase Cα deletion causes hypotension and decreased vascular contractility', Journal of hypertension, vol. 36, no. 3, pp. 510-519. https://doi.org/10.1097/HJH.0000000000001596
Wynne, Brandi M. ; McCarthy, Cameron G. ; Szasz, Theodora ; Molina, Patrick A. ; Chapman, Arlene B. ; Webb, R Clinton ; Klein, Janet D. ; Hoover, Robert S. / Protein kinase Cα deletion causes hypotension and decreased vascular contractility. In: Journal of hypertension. 2018 ; Vol. 36, No. 3. pp. 510-519.
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AU - Klein, Janet D.

AU - Hoover, Robert S.

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