Vasoconstriction and increased flow: two principal mechanisms of shear stress-dependent endothelial autacoid release.
The mechanisms of which nitric oxide (NO) and prostacyclin (PGI2) are released from endothelium-intact rabbit femoral arteries under resting conditions and after stimulation by either shear stress or acetylcholine (ACh) were investigated. The concentration of NO in the effluate was determined by monitoring the NO-mediated stimulation of purified soluble guanylyl cyclase, and that of PGI2 was done using a specific radioimmunoassay for its stable hydrolysis product, 6-ketoprostaglandin F1 alpha, NO release under static (no-flow) conditions and in the absence of a stimulus accounted for 10-15% of the maximum release of NO from luminally perfused segments stimulated with ACh and was attenuated by removal of extracellular Ca2+. A six- to sevenfold increase in shear stress (from 0.15 to 1 dyn/cm2), generated either by vasoconstriction at constant flow or by an increase in flow at constant diameter, elicited a five- to sevenfold increase in NO release, which was correlated with increasing shear stress. The same increase in shear stress also enhanced the release of PGI2 from the femoral artery segments by 11- to 12-fold. Removal of extracellular Ca2+ abolished the shear stress-dependent PGI2 released but did not affect that of NO. In contrast, the ACh-stimulated NO release was strongly inhibited in the absence of extracellular Ca2+ (78% inhibition). Charybdotoxin, an inhibitor of Ca(2+)-activated K+ channels, and glibenclamide, an inhibitor of the ATP-sensitive K+ channel, had no effect on the shear stress-dependent release of NO.(ABSTRACT TRUNCATED AT 250 WORDS)
Hecker
M
M
Institute of Applied Physiology, University of Freiburg, Germany.
Mülsch
A
A
Bassenge
E
E
Busse
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D012898:Autacoids / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005263:Femoral Artery / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011134:Polysaccharides / Q000502:physiology; D011817:Rabbits; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D014661:Vasoconstriction / Q000502:physiology*
D012898:Autacoids; D006023:Glycoproteins; D011134:Polysaccharides; D009569:Nitric Oxide; D011464:Epoprostenol; D000109:Acetylcholine; D002118:Calcium