Abolition of flow-dependent EDRF release before that evoked by agonists in hypercholesterolaemic XXXX .

@entity534 @entity95 @entity165 @entity934
1. We have used a pulsatile cascade bioassay system to investigate the effects of dietary-induced hypercholesterolaemia on EDRF release evoked by @entity934 and by the oscillatory and time-averaged components of flow, in isolated segments of @entity95 abdominal aorta. 2. Flow pulsatility (frequency range 0.1-10 Hz) was studied with constant flow (9 ml min-1) at a pulse pressure amplitude of 2 mmHg. Frequency-related EDRF release, maximal at 6 Hz, was slightly attenuated after 4 weeks and abolished after 8 weeks of @entity165 feeding. 3. Time-averaged shear stress was manipulated with dextran (1-4% w/v, 80000 mol. wt.), to increase perfusate viscosity. EDRF release induced by increased perfusate viscosity was unaffected after 4 weeks but abolished after 8 weeks of @entity165 feeding. 4. Endothelium-dependent relaxations to @entity934 (0.1-10 microM) were not influenced after 4 weeks and only partially attenuated (by 60% of the maximal response, EC50 unchanged at 6.45 +/- 0.04 vs. 6.4 +/- 0.1 microM) after 8 weeks of @entity165 feeding. 5. Blood @entity165 levels were significantly (P < 0.001) increased after 4 weeks (26 +/- 3.6 vs 2.6 +/- 0.6 mmol l-1) and 8 weeks (56.2 +/- 3.8 vs 1.3 +/- 0.1 mmol l-1) of @entity165 feeding but after 8 weeks plasma @entity534 levels were not significantly different from the age-matched controls (0.2 +/- 0.05 vs. 0.19 +/- 0.04 mmol l-1). 6. We conclude that hypercholesterolaemia impairs flow-related (pulsatile- and time-averaged shear-induced) EDRF release earlier than @entity934 -induced relaxation in @entity95 aorta. This is consistent with the view that different transduction mechanisms mediate EDRF release in response to agonists and flow.
