Endothelium-dependent relaxation, cholesterol content and high energy metabolite balance in Watanabe hyperlipemic rabbit aorta.
Functional and metabolic parameters of thoracic aorta from Watanabe heritable hyperlipemic (WHHL) rabbits (aged 11-14 months) were investigated in vitro. The aortic preparations, normally responsive to noradrenaline, showed a diminished response to the endothelium-dependent agent, acetylcholine, in comparison with control preparations from age-matched New Zealand rabbits (maximal relaxation: 33 +/- 4% in WHHL vs. 52 +/- 2% in controls: P less than 0.005). ATP relaxant effect (only partially endothelium-dependent) was unimpaired in WHHL aorta, and it was much higher than in controls (maximal response: 63 +/- 6% vs. 37 +/- 3%, respectively; P less than 0.005). The response to NaNO2, an endothelium-independent relaxant, was unchanged in WHHL aortas. Acetylcholine-induced response was found to be inversely related to the degree of total cholesterol infiltration in aorta (r = -0.62, P less than 0.05). No correlation was observed between either total serum cholesterol or triglycerides and ACh-induced response. Furthermore, the concentration of adenine nucleotides and nucleosides in the aortic tissue of WHHL rabbits was lower than in controls, indicating a loss of energy balance. The results indicate a functional damage induced by genetic hyperlipidemia on endothelium-dependent relaxation and an impairment of energy-rich phosphate metabolism of the aortic wall. The relationship between functional and metabolic parameters is not yet clarified.
Ragazzi
E
E
Dept. of Pharmacology, Padua University, Italy.
Chinellato
A
A
De Biasi
M
M
Pandolfo
L
L
Prosdocimi
M
M
Norido
F
F
Caparrotta
L
L
Fassina
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000502:physiology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism; D005260:Female; D006949:Hyperlipidemias / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D002784:Cholesterol