Regulation of secretion and clearance of C-type natriuretic peptide in the interaction of vascular endothelial cells and smooth muscle cells

Yasato Komatsu, Hiroshi Itoh, Shin Ichi Suga, Toshio Igaki, Yoshihiro Ogawa, Ichiro Kishimoto, Osamu Nakagawa, Takaaki Yoshimasa, Kazuwa Nakao

Research output: Contribution to journalArticle

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Abstract

Objective. To clarify the significance of C-type natriuretic peptide in the interaction between endothelial cells and vascular smooth muscle cells by investigating the endothelial production of C-type natriuretic peptide and the clearance mechanism of C-type natriuretic peptide using the endothelial cells-smooth muscle cells co-culture system. Results. Secretion of C-type natriuretic peptide in the direct co-culture of endothelial cells with smooth muscle cells elicited as much as a 60-fold increase compared with endothelial cells alone. The accumulation of intracellular cyclic GMP in the co-culture was consequently increased and the elevation of cyclic GMP level in the co-culture was abolished by the anti-C-type natriuretic peptide monoclonal antibody. The elevated cyclic GMP production in the co-culture was abolished by the anti-transforming growth factor-β neutralizing antibody. Candoxatrilat (10-6-10-4 mol/l), a neutral endopeptidase inhibitor, dose-dependently increased the concentrations of C-type natriuretic peptide in the culture medium with endothelial cells alone, but not in the endothelial cells-smooth muscle cells co-culture. The transcript of neutral endopeptidase messenger RNA was detected in endothelial cells but not in smooth muscle cells by reverse transcriptase polymerase chain reaction. Treatment with C-atrial natriuretic factor (10-9-10-6 mol/l), the specific ligand for the clearance receptor of the natriuretic peptides, resulted in dose-dependent augmentation of C-type natriuretic peptide concentration and concomitant intracellular cyclic GMP production in the endothelial cells-smooth muscle cells co-culture but not in endothelial cells alone. Conclusion. The present study demonstrated that direct interaction between endothelial cells and smooth muscle cells augments C-type natriuretic peptide secretion from endothelial cells through transforming growth factor-β activation, and revealed that the enzymatic degradation is responsible for the steady state level of C-type natriuretic peptide in endothelial cells alone and that the receptor-mediated clearance mainly determines the augmented level of C-type natriuretic peptide in the interaction between endothelial cells and smooth muscle cells. The results taken together raise the possibility that endothelial C-type natriuretic peptide might play a role in regulation of vascular tone and remodelling.

Original languageEnglish
Pages (from-to)585-592
Number of pages8
JournalJournal of hypertension
Volume14
Issue number5
DOIs
Publication statusPublished - Jun 7 1996

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C-Type Natriuretic Peptide
Smooth Muscle Myocytes
Endothelial Cells
Coculture Techniques
Cyclic GMP
Neprilysin
Cell Culture Techniques
Transforming Growth Factors
Natriuretic Peptides
Atrial Natriuretic Factor
Neutralizing Antibodies
Protease Inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Vascular Smooth Muscle

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Regulation of secretion and clearance of C-type natriuretic peptide in the interaction of vascular endothelial cells and smooth muscle cells. / Komatsu, Yasato; Itoh, Hiroshi; Suga, Shin Ichi; Igaki, Toshio; Ogawa, Yoshihiro; Kishimoto, Ichiro; Nakagawa, Osamu; Yoshimasa, Takaaki; Nakao, Kazuwa.

In: Journal of hypertension, Vol. 14, No. 5, 07.06.1996, p. 585-592.

Research output: Contribution to journalArticle

Komatsu, Yasato ; Itoh, Hiroshi ; Suga, Shin Ichi ; Igaki, Toshio ; Ogawa, Yoshihiro ; Kishimoto, Ichiro ; Nakagawa, Osamu ; Yoshimasa, Takaaki ; Nakao, Kazuwa. / Regulation of secretion and clearance of C-type natriuretic peptide in the interaction of vascular endothelial cells and smooth muscle cells. In: Journal of hypertension. 1996 ; Vol. 14, No. 5. pp. 585-592.
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AU - Itoh, Hiroshi

AU - Suga, Shin Ichi

AU - Igaki, Toshio

AU - Ogawa, Yoshihiro

AU - Kishimoto, Ichiro

AU - Nakagawa, Osamu

AU - Yoshimasa, Takaaki

AU - Nakao, Kazuwa

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N2 - Objective. To clarify the significance of C-type natriuretic peptide in the interaction between endothelial cells and vascular smooth muscle cells by investigating the endothelial production of C-type natriuretic peptide and the clearance mechanism of C-type natriuretic peptide using the endothelial cells-smooth muscle cells co-culture system. Results. Secretion of C-type natriuretic peptide in the direct co-culture of endothelial cells with smooth muscle cells elicited as much as a 60-fold increase compared with endothelial cells alone. The accumulation of intracellular cyclic GMP in the co-culture was consequently increased and the elevation of cyclic GMP level in the co-culture was abolished by the anti-C-type natriuretic peptide monoclonal antibody. The elevated cyclic GMP production in the co-culture was abolished by the anti-transforming growth factor-β neutralizing antibody. Candoxatrilat (10-6-10-4 mol/l), a neutral endopeptidase inhibitor, dose-dependently increased the concentrations of C-type natriuretic peptide in the culture medium with endothelial cells alone, but not in the endothelial cells-smooth muscle cells co-culture. The transcript of neutral endopeptidase messenger RNA was detected in endothelial cells but not in smooth muscle cells by reverse transcriptase polymerase chain reaction. Treatment with C-atrial natriuretic factor (10-9-10-6 mol/l), the specific ligand for the clearance receptor of the natriuretic peptides, resulted in dose-dependent augmentation of C-type natriuretic peptide concentration and concomitant intracellular cyclic GMP production in the endothelial cells-smooth muscle cells co-culture but not in endothelial cells alone. Conclusion. The present study demonstrated that direct interaction between endothelial cells and smooth muscle cells augments C-type natriuretic peptide secretion from endothelial cells through transforming growth factor-β activation, and revealed that the enzymatic degradation is responsible for the steady state level of C-type natriuretic peptide in endothelial cells alone and that the receptor-mediated clearance mainly determines the augmented level of C-type natriuretic peptide in the interaction between endothelial cells and smooth muscle cells. The results taken together raise the possibility that endothelial C-type natriuretic peptide might play a role in regulation of vascular tone and remodelling.

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