Nitric oxide sensitivity in pulmonary artery and airway smooth muscle

A possible role for cGMP responsiveness

Miwa Taniguchi, Younglan Kwak, Keith A. Jones, David O. Warner, William J. Perkins

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We aimed to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Porcine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used in concentration-response studies to the NO donor (Z)-1-[N-2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM consistently exhibited greater relaxation at a given DETA-NO concentration (NO responsiveness) than TSM NO responsiveness, with DETA-NO log EC50 being -6.55 ± 0.11 and -5.37 ± 0.13 for PASM and TSM, respectively (P < 0.01). We determined relationships between tissue cGMP concentration ([cGMP]i) and relaxation using the particulate guanylyl cyclase agonist atrial natriuretic peptide. Atrial natriuretic peptide resulted in nearly complete relaxation, with no detectable increase in [cGMP]i in PASM and only 20% relaxation (10-fold increase in [cGMP]i) in TSM, indicating that TSM is less cGMP responsive than PASM. Total cGMP-dependent protein kinase I (cGKI) mRNA expression was greater in PASM than in TSM (2.23 ± 0.36 vs. 0.93 ± 0.31 amol mRNA/μg total RNA, respectively; P < 0.01), but total cGKI protein expression was not significantly different (0.56 ± 0.07 and 0.49 ± 0.04 ng cGKI/μg protein, respectively). The phosphotransferase assay for the soluble fraction of tissue homogenates demonstrated no difference in the cGMP EC 50 between PASM and TSM. The maximal phosphotransferase activityindexed to the amount of total cGKI in the homogenate differed significantly between PASM and TSM (1.61 ± 0.15 and 1.04 ± pmol·min-1·ng cGKI-1, respectively; P < 0.05), suggesting that cGKI may be regulated differently in the two tissues. A novel intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is thus greater cGMP responsiveness from increased cGKI-specific activity in PASM.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume290
Issue number5
DOIs
Publication statusPublished - 2006 May 1

Fingerprint

Pulmonary Artery
Smooth Muscle
Nitric Oxide
Cyclic GMP-Dependent Protein Kinase Type I
DEET
Atrial Natriuretic Factor
Phosphotransferases
Messenger RNA
Nitric Oxide Donors
Guanylate Cyclase

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

@article{cf8ca89048e349e0aabcb91056e8b74f,
title = "Nitric oxide sensitivity in pulmonary artery and airway smooth muscle: A possible role for cGMP responsiveness",
abstract = "We aimed to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Porcine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used in concentration-response studies to the NO donor (Z)-1-[N-2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM consistently exhibited greater relaxation at a given DETA-NO concentration (NO responsiveness) than TSM NO responsiveness, with DETA-NO log EC50 being -6.55 ± 0.11 and -5.37 ± 0.13 for PASM and TSM, respectively (P < 0.01). We determined relationships between tissue cGMP concentration ([cGMP]i) and relaxation using the particulate guanylyl cyclase agonist atrial natriuretic peptide. Atrial natriuretic peptide resulted in nearly complete relaxation, with no detectable increase in [cGMP]i in PASM and only 20{\%} relaxation (10-fold increase in [cGMP]i) in TSM, indicating that TSM is less cGMP responsive than PASM. Total cGMP-dependent protein kinase I (cGKI) mRNA expression was greater in PASM than in TSM (2.23 ± 0.36 vs. 0.93 ± 0.31 amol mRNA/μg total RNA, respectively; P < 0.01), but total cGKI protein expression was not significantly different (0.56 ± 0.07 and 0.49 ± 0.04 ng cGKI/μg protein, respectively). The phosphotransferase assay for the soluble fraction of tissue homogenates demonstrated no difference in the cGMP EC 50 between PASM and TSM. The maximal phosphotransferase activityindexed to the amount of total cGKI in the homogenate differed significantly between PASM and TSM (1.61 ± 0.15 and 1.04 ± pmol·min-1·ng cGKI-1, respectively; P < 0.05), suggesting that cGKI may be regulated differently in the two tissues. A novel intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is thus greater cGMP responsiveness from increased cGKI-specific activity in PASM.",
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Nitric oxide sensitivity in pulmonary artery and airway smooth muscle : A possible role for cGMP responsiveness. / Taniguchi, Miwa; Kwak, Younglan; Jones, Keith A.; Warner, David O.; Perkins, William J.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 290, No. 5, 01.05.2006.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nitric oxide sensitivity in pulmonary artery and airway smooth muscle

T2 - A possible role for cGMP responsiveness

AU - Taniguchi, Miwa

AU - Kwak, Younglan

AU - Jones, Keith A.

AU - Warner, David O.

AU - Perkins, William J.

PY - 2006/5/1

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N2 - We aimed to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Porcine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used in concentration-response studies to the NO donor (Z)-1-[N-2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM consistently exhibited greater relaxation at a given DETA-NO concentration (NO responsiveness) than TSM NO responsiveness, with DETA-NO log EC50 being -6.55 ± 0.11 and -5.37 ± 0.13 for PASM and TSM, respectively (P < 0.01). We determined relationships between tissue cGMP concentration ([cGMP]i) and relaxation using the particulate guanylyl cyclase agonist atrial natriuretic peptide. Atrial natriuretic peptide resulted in nearly complete relaxation, with no detectable increase in [cGMP]i in PASM and only 20% relaxation (10-fold increase in [cGMP]i) in TSM, indicating that TSM is less cGMP responsive than PASM. Total cGMP-dependent protein kinase I (cGKI) mRNA expression was greater in PASM than in TSM (2.23 ± 0.36 vs. 0.93 ± 0.31 amol mRNA/μg total RNA, respectively; P < 0.01), but total cGKI protein expression was not significantly different (0.56 ± 0.07 and 0.49 ± 0.04 ng cGKI/μg protein, respectively). The phosphotransferase assay for the soluble fraction of tissue homogenates demonstrated no difference in the cGMP EC 50 between PASM and TSM. The maximal phosphotransferase activityindexed to the amount of total cGKI in the homogenate differed significantly between PASM and TSM (1.61 ± 0.15 and 1.04 ± pmol·min-1·ng cGKI-1, respectively; P < 0.05), suggesting that cGKI may be regulated differently in the two tissues. A novel intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is thus greater cGMP responsiveness from increased cGKI-specific activity in PASM.

AB - We aimed to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Porcine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used in concentration-response studies to the NO donor (Z)-1-[N-2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM consistently exhibited greater relaxation at a given DETA-NO concentration (NO responsiveness) than TSM NO responsiveness, with DETA-NO log EC50 being -6.55 ± 0.11 and -5.37 ± 0.13 for PASM and TSM, respectively (P < 0.01). We determined relationships between tissue cGMP concentration ([cGMP]i) and relaxation using the particulate guanylyl cyclase agonist atrial natriuretic peptide. Atrial natriuretic peptide resulted in nearly complete relaxation, with no detectable increase in [cGMP]i in PASM and only 20% relaxation (10-fold increase in [cGMP]i) in TSM, indicating that TSM is less cGMP responsive than PASM. Total cGMP-dependent protein kinase I (cGKI) mRNA expression was greater in PASM than in TSM (2.23 ± 0.36 vs. 0.93 ± 0.31 amol mRNA/μg total RNA, respectively; P < 0.01), but total cGKI protein expression was not significantly different (0.56 ± 0.07 and 0.49 ± 0.04 ng cGKI/μg protein, respectively). The phosphotransferase assay for the soluble fraction of tissue homogenates demonstrated no difference in the cGMP EC 50 between PASM and TSM. The maximal phosphotransferase activityindexed to the amount of total cGKI in the homogenate differed significantly between PASM and TSM (1.61 ± 0.15 and 1.04 ± pmol·min-1·ng cGKI-1, respectively; P < 0.05), suggesting that cGKI may be regulated differently in the two tissues. A novel intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is thus greater cGMP responsiveness from increased cGKI-specific activity in PASM.

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