Original Research: Role of phosphodiesterases in modulation of BKCa channels in hypertensive pulmonary arterial smooth muscle

Shu Zhu, Richard E. White, Scott A. Barman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BKCa channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BKCa channels, but little is known about PKC-mediated modulation of BKCa channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BKCa channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BKCa 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 BKCa 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 - Jun 2008

Fingerprint

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

@article{7c15e99288ed45d18ceb2869c7e09b2c,
title = "Original Research: Role of phosphodiesterases in modulation of BKCa channels in hypertensive pulmonary arterial smooth muscle",
abstract = "BKCa channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BKCa channels, but little is known about PKC-mediated modulation of BKCa channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BKCa channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BKCa 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 BKCa channels and causes pulmonary vasoconstriction in hypertensive pulmonary arterial smooth muscle via PDE, which further suggests PDE inhibitors for treatment of pulmonary hypertension.",
keywords = "BKCa channels, PKC, cAMP, phosphodiesterase, pulmonary",
author = "Shu Zhu and White, {Richard E.} and Barman, {Scott A.}",
year = "2008",
month = "6",
doi = "10.1177/1753465808091327",
language = "English (US)",
volume = "2",
pages = "119--127",
journal = "Therapeutic Advances in Respiratory Disease",
issn = "1753-4658",
publisher = "SAGE Publications Ltd",
number = "3",

}

TY - JOUR

T1 - Original Research

T2 - Role of phosphodiesterases in modulation of BKCa channels in hypertensive pulmonary arterial smooth muscle

AU - Zhu, Shu

AU - White, Richard E.

AU - Barman, Scott A.

PY - 2008/6

Y1 - 2008/6

N2 - BKCa channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BKCa channels, but little is known about PKC-mediated modulation of BKCa channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BKCa channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BKCa 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 BKCa channels and causes pulmonary vasoconstriction in hypertensive pulmonary arterial smooth muscle via PDE, which further suggests PDE inhibitors for treatment of pulmonary hypertension.

AB - BKCa channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BKCa channels, but little is known about PKC-mediated modulation of BKCa channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BKCa channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BKCa 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 BKCa channels and causes pulmonary vasoconstriction in hypertensive pulmonary arterial smooth muscle via PDE, which further suggests PDE inhibitors for treatment of pulmonary hypertension.

KW - BKCa channels

KW - PKC

KW - cAMP

KW - phosphodiesterase

KW - pulmonary

UR - http://www.scopus.com/inward/record.url?scp=68749101239&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68749101239&partnerID=8YFLogxK

U2 - 10.1177/1753465808091327

DO - 10.1177/1753465808091327

M3 - Article

C2 - 19124364

AN - SCOPUS:68749101239

VL - 2

SP - 119

EP - 127

JO - Therapeutic Advances in Respiratory Disease

JF - Therapeutic Advances in Respiratory Disease

SN - 1753-4658

IS - 3

ER -