Keiko Takahashi, Mitsumasa Ohyanagi, Kiyomitsu Ikeoka and Tadaaki Iwasaki
The First Department of Internal Medicine, Hyogo College of Medicine,
1 - 1, Mukogawa-cho, Nishinomiya, Hyogo 663 - 8501, Japan
Abstract: The extent to which reported abnormal responses of
the human coronary circulation to acetylcholine in patients with hypercholesterolemia
reflect endothelial injury is not clear. We used an in vitro rabbit model
to determine whether these reactions involve endothelial or vascular smooth
muscle dysfunction. Coronary resistance arterioles were isolated from hearts
of rabbits fed 1% cholesterol to induce hypercholesterolemia or a control
diet for 4 weeks. Arterioles were double cannulated with glass micropipettes
and pressurized in a no-flow state. Acetylcholine contracted the arterioles
in a concentration-dependent manner whether or not the nitric oxide synthase
inhibitor NG-monomethyl-l-arginine was added. In control
but not hypercholesterolemic preparations, contraction was significantly
greater when endothelium was removed. In the hypercholesterolemic group,
contraction significantly exceeded that in controls. In control but not
high-cholesterol preparations, substance P dilated vessels with intact endothelium
in a concentration-dependent manner. Addition of NG-monomethyl-l-arginine
inhibited this response. With or without endothelium, norepinephrine contracted
arterioles to a greater extent in the hypercholesterolemic group than in
controls. We concluded that severe hypercholesterolemia decreased endothelially
dependent factors by injuring endothelium and independently increased contractility
of vascular smooth muscle.
Keywords: Acetylcholine, Coronary resistance arteriole, Hypercholesterolemia,
Vascular smooth muscle, Endothelium