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Relationship between functional and metabolic parameters in aorta from watanabe hyperlipemic (WHHL) Rabbits
Pharmacological Research, Vol. 22, Supplement 2, 1990
81
RELATIONSHIP BETWEEN FUNCTIONAL AND METABOLIC PARAMETERS IN AORTA l$0M WATANABE HYPERLIPEMIC (WHHL) RABBITS
L. Caparrotta. A. Chinellato. M. De Biasi. G. Fassina, L. Pandolfo and E. Raqazzi Department of Pharmacology, Largo E. Meneghetti 2, University of Padua, 1-35131 Padova (Italy) In this study the functional response of WHHL aortas to vasodi 1ators was tentatively correl ated with high energy adenine nucleotides, nucleosides and purine turnover with regard to the role of ATP and adenosine in the regulation of blood vessel function. Functional and metabolic parameters of thoracic aorta from WHHL rabbits (aged 11-14 months) were investigated in vitro and compared to those in normal age-matched New Zealand rabbits. The aort ic preparations, normally responsive to noradrenaline, showed a diminished response to the endothelium-dependent agent, acetylcholine, in comparison with control preparations from agematched New Zealand rabbi ts (maximal relaxation: 33 + 4% in WHHL vs. 52 + 2% in controls; P< 0.005) . ATP relaxant effect (only partiall~ endothelium-dependent) was unimpaired in WHHL aorta , and it was much higher than in controls (maximal response: 63 ~ 6% vs. 37 ~ 3%, respectively; P< 0.005). The response to NaN02, an endothelium-independent relaxant, was unchanged in WHHL aortas . Acethylcholine-induced response was found to be inversely related to the degree of total cholesterol infiltration in aorta ( r= -0.62, P< 0.05). No correlation was observed between either total serum cholesterol or triglycerides and ACh-induced response. Furthermore, the concentration of aden ine 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. Thus, WHHL rabbits represent an interesting tool for the study not only of the morpho-cytological progression of atherosclerosis but also of the relationship between functional parameters and energy metabolism.
1043-6618/90/22110081-01 / $03.00/0
© 1990 Th e Italian Pharmaco logical Society
81
RELATIONSHIP BETWEEN FUNCTIONAL AND METABOLIC PARAMETERS IN AORTA l$0M WATANABE HYPERLIPEMIC (WHHL) RABBITS
L. Caparrotta. A. Chinellato. M. De Biasi. G. Fassina, L. Pandolfo and E. Raqazzi Department of Pharmacology, Largo E. Meneghetti 2, University of Padua, 1-35131 Padova (Italy) In this study the functional response of WHHL aortas to vasodi 1ators was tentatively correl ated with high energy adenine nucleotides, nucleosides and purine turnover with regard to the role of ATP and adenosine in the regulation of blood vessel function. Functional and metabolic parameters of thoracic aorta from WHHL rabbits (aged 11-14 months) were investigated in vitro and compared to those in normal age-matched New Zealand rabbits. The aort ic preparations, normally responsive to noradrenaline, showed a diminished response to the endothelium-dependent agent, acetylcholine, in comparison with control preparations from agematched New Zealand rabbi ts (maximal relaxation: 33 + 4% in WHHL vs. 52 + 2% in controls; P< 0.005) . ATP relaxant effect (only partiall~ endothelium-dependent) was unimpaired in WHHL aorta , and it was much higher than in controls (maximal response: 63 ~ 6% vs. 37 ~ 3%, respectively; P< 0.005). The response to NaN02, an endothelium-independent relaxant, was unchanged in WHHL aortas . Acethylcholine-induced response was found to be inversely related to the degree of total cholesterol infiltration in aorta ( r= -0.62, P< 0.05). No correlation was observed between either total serum cholesterol or triglycerides and ACh-induced response. Furthermore, the concentration of aden ine 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. Thus, WHHL rabbits represent an interesting tool for the study not only of the morpho-cytological progression of atherosclerosis but also of the relationship between functional parameters and energy metabolism.
1043-6618/90/22110081-01 / $03.00/0
© 1990 Th e Italian Pharmaco logical Society