Mitogen-activated protein kinase contributes to elevated basal tone in aortic smooth muscle from hypertensive rats

Junghwan Kim1, Youn R Lee, Chang-Hun Lee

  • 1Department of Physiology, College of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Danwol-dong 322, Choongju 380-701, Korea.

Insights

Mitogen-activated protein kinase (MAPK) pathway activation elevates basal vascular tone in deoxycorticosterone acetate (DOCA)-salt hypertension. This process is regulated by protein kinase C (PKC), not Rho kinase or calcium channels.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Biology
  • Pharmacology

Background:

  • Hypertension is characterized by elevated vascular tone.
  • The signaling pathways contributing to sustained increases in vascular tone are not fully understood.
  • Mitogen-activated protein kinase (MAPK) pathways are implicated in vascular smooth muscle function.

Purpose of the Study:

  • To investigate the role of MAPK/extracellular signal-regulated protein kinase (ERK) in elevated basal vascular tone in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.
  • To elucidate the upstream regulators of MAPK/ERK activation in this hypertensive model.

Main Methods:

  • Aortic smooth muscle strips from DOCA-salt hypertensive and sham-operated rats were used.
  • The effects of specific inhibitors (PD098059 for MAPK/ERK kinase, GF109203X for protein kinase C (PKC), Y27632 for Rho kinase, verapamil for Ca2+ channels) on basal tone and ERK1/2 activation were assessed.
  • Western blotting was used to measure ERK1/2 activation levels.

Main Results:

  • The MAPK/ERK kinase inhibitor PD098059 dose-dependently inhibited basal tone and ERK1/2 activation in DOCA-salt hypertensive rats.
  • Basal ERK1/2 activation was significantly higher in hypertensive rats compared to controls.
  • PKC inhibition (GF109203X) reduced both basal tone and ERK1/2 activity in hypertensive rats.
  • Rho kinase (Y27632) and Ca2+ channel (verapamil) inhibition reduced basal tone but did not affect ERK1/2 activity.

Conclusions:

  • Elevated basal vascular tone in DOCA-salt hypertension is mediated by altered MAPK/ERK activation.
  • Protein kinase C (PKC) plays a regulatory role in this MAPK-dependent pathway.
  • Rho kinase and intracellular calcium do not appear to be the primary regulators of basal tone in this model.

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