Natriuretic Peptide-Augmented Induction of Nitric Oxide Synthase through Cyclic Guanosine 3′,5′-Monophosphate Elevation in Vascular Smooth Muscle Cells

Takeshi Marumo, Toshio Nakaki, Keiichi Hishikawa, Junichi Hirahashi, Hiromichi Suzuki, Ryuichi Kato, Takao Saruta

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

To elucidate the role of natriuretic peptides in vascular remodeling, the effects of atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide (CNP) on the induction of inducible nitric oxide (NO) synthase (iNOS) in rat aortic smooth muscle cells were examined. Although none of the peptides when applied alone induced the production of nitrite, a stable end product of NO, each peptide dramatically enhanced nitrite production induced by a cytokine combination of interleukin-1α and tumor necrosis factor-α. Each natriuretic peptide stimulated intracellular cGMP accumulation in a dose-dependent manner. Time-dependent nitrite production by the cytokines was increased by CNP cotreatment and inhibited by NG-methyl-L-arginine, indicating involvement of the L-arginine-NO pathway. Northern blot analysis showed that the augmented nitrite production was accompanied by an increase in iNOS messenger RNA. A cGMP analog, 8-bromo-cGMP, completely mimicked all of the effects of CNP described above. A cGMP-dependent protein kinase inhibitor, KT5823, paradoxically increased nitrite production and iNOS messenger RNA levels induced by the combination of 8-bromo-cGMP and both cytokines or by the two cytokines only. These data demonstrate the stimulatory effect of cGMP on cytokine-induced iNOS and imply that natriuretic peptides may play a regulatory role in vascular remodeling via the production of large amounts of NO.

Original languageEnglish
Pages (from-to)2135-2142
Number of pages8
JournalEndocrinology
Volume136
Issue number5
Publication statusPublished - 1995

Fingerprint

Guanosine Monophosphate
Natriuretic Peptides
Nitrites
Vascular Smooth Muscle
Nitric Oxide Synthase
Smooth Muscle Myocytes
C-Type Natriuretic Peptide
Cytokines
Nitric Oxide
Arginine
Cyclic GMP-Dependent Protein Kinases
Messenger RNA
Peptides
Brain Natriuretic Peptide
Atrial Natriuretic Factor
Nitric Oxide Synthase Type II
Protein Kinase Inhibitors
Interleukin-1
Northern Blotting
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Natriuretic Peptide-Augmented Induction of Nitric Oxide Synthase through Cyclic Guanosine 3′,5′-Monophosphate Elevation in Vascular Smooth Muscle Cells. / Marumo, Takeshi; Nakaki, Toshio; Hishikawa, Keiichi; Hirahashi, Junichi; Suzuki, Hiromichi; Kato, Ryuichi; Saruta, Takao.

In: Endocrinology, Vol. 136, No. 5, 1995, p. 2135-2142.

Research output: Contribution to journalArticle

Marumo, Takeshi ; Nakaki, Toshio ; Hishikawa, Keiichi ; Hirahashi, Junichi ; Suzuki, Hiromichi ; Kato, Ryuichi ; Saruta, Takao. / Natriuretic Peptide-Augmented Induction of Nitric Oxide Synthase through Cyclic Guanosine 3′,5′-Monophosphate Elevation in Vascular Smooth Muscle Cells. In: Endocrinology. 1995 ; Vol. 136, No. 5. pp. 2135-2142.
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