Accumulation of endogenous inhibitors for nitric oxide synthesis and decreased content of L‐arginine in regenerated endothelial cells

Article date: July 1995

By: Hiroshi Azuma, Jun Sato, Hidehisa Hamasaki, Akiko Sugimoto, Eiji Isotani, Satoshi Obayashi, in Volume 115, Issue 6, pages 1001-1004

We examined regeneration of endothelial cells (ECs), neointima formation, decreased endothelium‐dependent relaxation (EDR) and changes in the contents of L‐arginine, NG–monomethyl‐L‐arginine (l‐NMMA), asymmetrical NG, NG–dimethylarginine (ADMA) and symmetrical NG, NG–dimethylarginine (SDMA) in the regnerated ECs, 6 weeks after balloon denudation of the rabbit carotid artery.

Regeneration of ECs was completed in 6 weeks and a significant neointima formation accompanied by the decreased EDR was observed.

L‐NMMA and ADMA contents in the regenerated ECs (23.5 ± 4.3 and 21.2 ± 2.0 pmol mg−1 DNA, respectively) were significantly (P<0.05 and P<0.01) higher than those in the control ECs (8.8 ± 3.0 and 7.4plusmn;1.9 pmol mg−1 DNA, respectively), whereas L‐arginine was significantly (P< 0.005) decreased in the regenerated ECs (31,470±1,050 pmol mg−1 DNA) as compared to that in the control ECs (47,870±1,890 pmol mg−1 DNA). SDMA content was below the assay limits.

L‐NMMA and ADMA, but not SDMA, inhibited the EDR induced by acetylcholine in a concentration‐dependent manner. The inhibition with L‐NMMA and ADMA was prevented by an addition of L‐arginine, but not by D‐arginine.

These results suggest that the accumulation of endogenous inhibitors for nitric oxide synthesis and decreased L‐arginine content are associated with decreased NO production/release from regenerated ECs and neointima formation.

We examined regeneration of endothelial cells (ECs), neointima formation, decreased endothelium‐dependent relaxation (EDR) and changes in the contents of L‐arginine, NG–monomethyl‐L‐arginine (l‐NMMA), asymmetrical NG, NG–dimethylarginine (ADMA) and symmetrical NG, NG–dimethylarginine (SDMA) in the regnerated ECs, 6 weeks after balloon denudation of the rabbit carotid artery.

Regeneration of ECs was completed in 6 weeks and a significant neointima formation accompanied by the decreased EDR was observed.

L‐NMMA and ADMA contents in the regenerated ECs (23.5 ± 4.3 and 21.2 ± 2.0 pmol mg−1 DNA, respectively) were significantly (P<0.05 and P<0.01) higher than those in the control ECs (8.8 ± 3.0 and 7.4plusmn;1.9 pmol mg−1 DNA, respectively), whereas L‐arginine was significantly (P< 0.005) decreased in the regenerated ECs (31,470±1,050 pmol mg−1 DNA) as compared to that in the control ECs (47,870±1,890 pmol mg−1 DNA). SDMA content was below the assay limits.

L‐NMMA and ADMA, but not SDMA, inhibited the EDR induced by acetylcholine in a concentration‐dependent manner. The inhibition with L‐NMMA and ADMA was prevented by an addition of L‐arginine, but not by D‐arginine.

These results suggest that the accumulation of endogenous inhibitors for nitric oxide synthesis and decreased L‐arginine content are associated with decreased NO production/release from regenerated ECs and neointima formation.

DOI: 10.1111/j.1476-5381.1995.tb15910.x

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