Dual Control by Nerves and Endothelial Cells of Arterial Blood Flow in Atherosclerosis
Changes in the responses of vessels taken from Watanabe Heritable Hyperlipidaemic (WHHL) rabbits during the development of atherosclerosis at 4, 6 and 12 months were compared with those of vessels from control New Zealand White (NZW) rabbits at equivalent ages.
In vessels with severe atherosclerotic lesions (e.g. thoracic aorta) endothelial-mediated vasodilatation is attenuated, while direct responses to vascular smooth muscle are little changed.
In most other vessels (including mesenteric, hepatic, ear, coronary and saphenous arteries), where over 90% of endothelial cells appeared normal, endothelial-mediated vasodilator responses to acetylcholine and substance P were enhanced by 12 months in WHHL rabbits, while direct muscle vasoconstrictor and vasodilator responses showed gradual decline. Control NZW rabbits showed decline in both endothelial-mediated and direct muscle responses during the same period.
The basilar artery from WHHL rabbits showed little morphological evidence of serious lesions in either endothelial cells or smooth muscle up to 12 months, although endothelium-mediated vasodilatation was enhanced. This suggests that morphological criteria for assessing atherosclerotic damage do not necessarily correlate with changes in function.
Diminished sympathetic nerve-mediated vasoconstriction was demonstrated in 12-month-old WHHL mesenteric and hepatic arteries, although there was no reduction in adrenoceptor-mediated muscle responses.
It is suggested that the enhanced endothelial-mediated responses in these vessels may explain the well-known ‘compensatory vasodilatation’ characteristic of enlarged vessels in early atherosclerosis in which the lumen is not diminished and may even be enhanced. Speculations are made about the mechanism of enhanced endothelial-mediated vasodilatation. It is suggested that reduced nerve-mediated contraction may be an additional ‘trophic’ response contributing to ‘compensatory vasodilatation’ in early atherosclerosis. This study reinforces the view that different vessels respond differently in atherosclerosis and that there are marked variations with age and between the sexes in the changes occurring in the same vessel.
KeywordsBasilar Artery Vasoactive Intestinal Polypeptide Early Atherosclerosis Direct Muscle Perivascular Nerve
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