Original Research

Role of phosphodiesterases in modulation of BK Ca channels in hypertensive pulmonary arterial smooth muscle

Shu Zhu, Richard E. White, Scott A Barman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BK Ca channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BK Ca channels, but little is known about PKC-mediated modulation of BK Ca channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BK Ca channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BK Ca channels in FHR PASMC, which was blocked by PKC activation, and reversed by the phosphodiesterase (PDE) inhibitors IBMX, milrinone, and zaprinast. PDE inhibition also blocked the vasoconstrictor response to PKC activation in FHR pulmonary arteries. These results indicate that PKC inhibits cAMP-induced activation of BK Ca channels and causes pulmonary vasoconstriction in hypertensive pulmonary arterial smooth muscle via PDE, which further suggests PDE inhibitors for treatment of pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalTherapeutic Advances in Respiratory Disease
Volume2
Issue number3
DOIs
StatePublished - Jan 1 2008

Fingerprint

Large-Conductance Calcium-Activated Potassium Channels
Phosphoric Diester Hydrolases
Protein Kinase C
Smooth Muscle
Lung
Research
Phosphodiesterase Inhibitors
Pulmonary Hypertension
Smooth Muscle Myocytes
Milrinone
1-Methyl-3-isobutylxanthine
Vasoconstrictor Agents
Colforsin
Vasoconstriction
Pulmonary Artery
Arterial Pressure
Animal Models

Keywords

  • BKCa channels
  • PKC
  • cAMP
  • phosphodiesterase
  • pulmonary

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology (medical)

Cite this

Original Research : Role of phosphodiesterases in modulation of BK Ca channels in hypertensive pulmonary arterial smooth muscle. / Zhu, Shu; White, Richard E.; Barman, Scott A.

In: Therapeutic Advances in Respiratory Disease, Vol. 2, No. 3, 01.01.2008, p. 119-127.

Research output: Contribution to journalArticle

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