Mechanical deformation of vessel wall and shear stress determine the basal release of endothelium-derived relaxing factor in the intact rabbit coronary vascular bed.
We investigated the mechanisms that are responsible for the basal release of endothelium-derived relaxing factor (EDRF), which is likely to be identical with nitric oxide, in the intact coronary circulation. The increase in cGMP content of platelets passing through the coronary bed of the isolated rabbit heart was used as an index of EDRF release. Platelet cGMP content after passage through the heart under control conditions (flow rate of 20 ml/min) amounted to 0.50 +/- 0.10 pmol/mg protein. Inhibition of endothelial nitric oxide synthesis by 30 microM NG-nitro-L-arginine (L-NNA) reduced this amount by more than 60%. Increasing flow rate from 20 ml/min to 40 and 60 ml/min led to flow-dependent dilation as reflected by the subsequent drop in perfusion pressure after an initial rise. The flow-dependent dilation was associated with a significant increase in the normalized platelet cGMP content. L-NNA abolished completely both the flow-dependent dilation and the increase in platelet cGMP content. Increasing shear stress by a strong vasoconstriction (1 nM endothelin-1) at constant flow was also accompanied by a 2.5-fold increase in platelet cGMP content. To investigate whether mechanical forces applied to the vascular wall by the myocardial contraction cycle were also a stimulus for EDRF release, cardiac arrest was induced by a continuous infusion of mepivacaine (final concentration, 0.02%). Under these conditions, a decrease in platelet cGMP content comparable to that after nitric oxide synthesis inhibition was observed in the arrested heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Institute of Applied Physiology, University of Freiburg, FRG.
D
D
Lamontagne
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U
Pohl
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R
Busse
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000201:enzymology; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000378:metabolism*; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D013314:Stress, Mechanical
D009569:Nitric Oxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP