Korean Circ J.  2003 Nov;33(11):1036-1043. 10.4070/kcj.2003.33.11.1036.

Influence of Vascular Endothelium in Contraction Induced by Phorbol Ester in Renal Hypertensive Rats

• Jeong SA
• Kim H
• Cha KH
• Jun JY
• Yoon PJ
• Yeum CH
• Park J
• Cho NS
• Hong SP

• KMID: 2145614
• DOI: http://doi.org/10.4070/kcj.2003.33.11.1036

Abstract

BACKGROUND AND OBJECTIVES
The vascular endothelium plays an important role in circulation, by modulating the contractile responses of the arterial smooth muscle. This study was aimed at investigating the possible role of the endothelium in the contractile response to phorbol 12, 13-dibutyrate (PDB) in chronic two-kidney, one clip (2K1C) hypertensive rats.
MATERIALS AND METHODS
2K1C hypertension was induced by clipping the left renal artery of the study rats, with age-matched rats receiving a sham treatment, which served as controls. The thoracic aortae were mounted in tissue baths to measure the isometric tension.
RESULTS
The PDB showed a dose-dependent contraction, with larger responses in the 2K1C hypertensive than the sham-clipped control rats. Nw-nitro-L-arginine (L-NNA) and methylene blue (MB) induced an increase in the tension in the presence of PDB, and the potentiating effects of L-NNA or MB were attenuated in the 2K1C rats as compared to the controls. Staurosporine, an inhibitor of protein kinase C, completely inhibited the contractile response to PDB, as well as enhancing the effects of L-NNA and MB. Removal of the endothelium abolished the contractile responses to L-NNA and MB in both the 2K1C and control rats. The relaxation responses to acetylcholine in the aortic rings precontracted with PDB were also attenuated in the 2K1C rats, and L-NNA prevented the effect of the acetylc-holine-induced relaxation. Indomethacin, glibenclamide and iberiotoxin did not affect the PDB responses in both the 2K1C and control rats.
CONCLUSION
These results indicate the endothelium plays an inhibitory role against PDB-induced contraction in rat aortae, by releasing nitric oxide, and the inhibitory role of the endothelium is impaired in 2K1C renal hypertension.

Keyword

Protein kinase C; Nitric oxide; Endothelium; Renal hypertension

MeSH Terms

Acetylcholine
Animals
Aorta
Aorta, Thoracic
Baths
Endothelium
Endothelium, Vascular*
Glyburide
Hypertension
Hypertension, Renal
Indomethacin
Methylene Blue
Muscle, Smooth
Nitric Oxide
Placebos
Protein Kinase C
Rats*
Relaxation
Renal Artery
Staurosporine
Acetylcholine
Glyburide
Indomethacin
Methylene Blue
Nitric Oxide
Placebos
Protein Kinase C
Staurosporine