Improvement of nitrergic relaxation by farnesol of the sphincter of Oddi from hypercholesterolaemic rabbits.
Field stimulation relaxed the rabbit sphincter of Oddi muscle rings after incubation with atropine (1 microM) and guanethidine (4 microM) with a threefold increase in tissue cyclic cGMP content, a response previously shown to be essentially nitrergic. Preparations from hypercholesterolaemic rabbits (1.5% dietary cholesterol load over 8 weeks increasing serum total cholesterol from pre-diet 1.4+/-0.3 to 22.6+/-3.8 mmol/l) exhibited contractions with no change in cyclic GMP content under the same conditions. The nitrergic relaxation was recaptured with a twofold increase in tissue cyclic GMP content in preparations from hypercholesterolaemic rabbits undergone a treatment with 30 microM/kg farnesol i.v. twice a day over the last 3 days of the dietary period. We conclude that farnesol treatment restores nitrergic relaxation of the sphincter of Oddi in hypercholesterolaemia.
Szilvassy
Z
Z
1st Department of Medicine, Albert Szent-Gyorgyi Medical University Szeged, Hungary. szilva@farmak.pote.hu
Sari
R
R
Nemeth
J
J
Nagy
I
I
Csati
S
S
Lonovics
J
J
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D005204:Farnesol / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology*; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D011817:Rabbits; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D009569:Nitric Oxide; D005204:Farnesol; D006152:Cyclic GMP