Long-term inhibition of NO synthesis promotes atherosclerosis in the hypercholesterolemic rabbit thoracic aorta. PGH2 does not contribute to impaired endothelium-dependent relaxation.

Abstract

We examined whether prostaglandin (PG) H2, as an endothelium-dependent contracting factor, or the disturbed production of endothelium-derived relaxing factor, impairs endothelium-dependent relaxation and whether long-term inhibition of nitric oxide (NO) synthesis aggravates atherosclerosis in hypercholesterolemic rabbits. Male New Zealand White rabbits were fed one of the following diets: (1) standard chow; (2) 2% cholesterol-supplemented chow; (3) standard chow with 80 micrograms/mL N omega-nitro-L-arginine methylester (L-NAME), an NO synthetase inhibitor, in their drinking water; or (4) 2% cholesterol-supplemented chow with 80 or 160 micrograms/mL L-NAME in their drinking water. The rabbits were fed these diets for 8 or 12 weeks. Then aortic rings were obtained, and changes in isometric tension were recorded. Intimal atherosclerotic areas of the thoracic aortas were subsequently measured by planimetry. The cholesterol-supplemented diet significantly impaired endothelium-dependent aortic relaxation to acetylcholine. Pretreatment with the thromboxane A2/PGH2 receptor antagonist ONO-3708 did not reverse this impaired response. Vessels from both normocholesterolemic and hypercholesterolemic rabbits given L-NAME showed more impaired endothelium-dependent relaxation than those from their dietary counterparts not given L-NAME. Morphometric analysis revealed marked enlargement of intimal atherosclerotic areas in aortas from L-NAME-treated hypercholesterolemic rabbits compared with those from untreated hypercholesterolemic rabbits. These findings suggest that PGH2 does not contribute to impaired endothelium-dependent relaxation and that long-term administration of L-NAME promotes atherosclerosis by inhibition of NO synthesis in the hypercholesterolemic rabbit thoracic aorta.

• Authors: K Naruse, K Shimizu, M Muramatsu, Y Toki, Y Miyazaki, K Okumura, H Hashimoto, T Ito
• Journal: Arteriosclerosis and thrombosis : a journal of vascular biology (Arterioscler Thromb) Vol. 14 Issue 5 Pg. 746-52 (May 1994) ISSN: 1049-8834 [Print] United States
• PMID: 8172852 (Publication Type: Journal Article)

Chemical References

• Prostaglandins H
• Nitric Oxide
• Prostaglandin H2
• Arginine
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Aorta, Thoracic (pathology)
• Arginine (analogs & derivatives, pharmacology)
• Arteriosclerosis (etiology)
• Endothelium, Vascular (physiology)
• Hypercholesterolemia (complications)
• Male
• NG-Nitroarginine Methyl Ester
• Nitric Oxide (physiology)
• Prostaglandin H2
• Prostaglandins H (physiology)
• Rabbits
• Vasodilation (drug effects)