This study was undertaken to examine the change of contractile responses to vasoactive agents by atherosclerosis in the rabbit aorta.
Twenty-two male Japanese albino rabbits were divided into three groups: animals in group C were fed a normal diet, rabbits in group H were fed with 1% cholesterol diet for 3 months, and group S animals were fed with 1% cholesterol diet for 4-6 months. Immediately after sacrifice by exsanguination, the thoracic aorta was carefully dissected, to avoid rubbing the endothelial cells, and cut into 4×25mm helical strips. The strips were suspended in Krebs-Ringer solution kept at 37°C, aerated with 95% O
2+5%CO
2, and placed in organ bath under 2gr. resting tension.
Isometric force induced by KCl, norepinephrine (NE), 5-hydroxytryptamine (5-HT), and histamine (His) was measured with a force displacement transducer. After contractile examination, the aorta was photographed to determine the extent of atherosclerotic lesions. The degree of the lesion was graded into four classes according to the area of atheromatous plaque. Group S was subdivided into four groups: group S1 (area of atherosclerosis. 0-25%), group S2 (26-50%), group S3 (51-75%), group S4 (76-100%). The relationship between vasocontractile responses and the extent of atherosclerosis in the aorta was investigated.
Maximum tension generated by KCl decreased in group S1 when compared with group C. There was no significant differences between groups C, H, S2, S3 and S4. Maximum tension developed by 5-HT in group H, S3 and S4 were the same level as in the group C, but those in groups S1 and S2 were significantly lower than those in group C. Maximum tension generated by His was higher in group H and lower in group S than in group C. There was no significant difference in maximum tension generated by NE between the six groups.
ED
50 (median effective concentration, as an index of sensitivity to vasoactive agents) to KCl was not found to be different between the six groups. ED
50 to 5-HT decreased according to the extension of atherosclerosis. ED
50 to His in the group S3, S4 was higher than in group C. This means that the aorta with severe atherosclerosis was more sensitive to 5-HT, and less sensitive to His.
V
max (maximum velocity of developed tension at the concentration of approximate ED
50) decreased significantly and T 1/2
max (time from initiation of tension developing to half maximum tension at ED
50) for the four agents was significantly prolonged in group S4.
These results suggest that the changes of vasocontractility in atherosclerotic rabbit aorta are induced by the alteration of drug-specific pathways such as receptors or calcium mobilization in cell membrane. This is because the change of vasoreactivites are different between the degree of atherosclerosis or vasoactive agents.
It is thought that the decrement of V
max and extension of T 1/2 in the atherosclerotic aorta resulted from the mechanical change in the aorta caused by atherosclerosis, such as intimal thickening or increased stiffness of the arterial matrix.
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