Several experimental studies have suggested that the vasodilatory effects of @entity460 channel blockers (CCBs) are due in part to an endothelium-dependent mechanism. However, it remains unknown whether CCBs directly augment liberation of endothelium-derived dilator substances such as @entity842 (NO) in the @entity1 vasculature. The aim of this study was to examine whether CCBs of several kinds directly increase the bioavailability of NO in forearm resistance vessels. Twenty-four healthy @entity1 (mean age 30 +/- 2 years) were randomly assigned to three study groups (n = 8 in each), and each group was assigned one of three first-generation CCBs ( @entity594 , @entity3360 , @entity3988 ). Subdepressor doses of CCBs [4, 8, 16, 24, and 36 ( @entity3988 only) nmol/min; for 2 min in each dose] were infused intra-arterially, and forearm blood flow (FBF) was determined plethysmographically. After control FBF responses to CCBs had been measured, a NO synthase inhibitor (N(G)-monomethyl-L-arginine: @entity7293 ) was infused intra-arterially, and the FBF response to CCBs was again determined. Further, as a positive control for NO stimulation, @entity934 ( @entity1617 ) was also examined before and after @entity7293 in each group. Systemic blood pressure and heart rate did not change significantly during the study protocol. The FBF responses to these CCBs did not differ before and after NO synthase inhibition by @entity7293 (FBF at maximum doses: @entity594 , 8.0 +/- 0.8 vs. 7.3 +/- 0.7; @entity3360 , 7.3 +/- 1.5 vs. 6.5 +/- 1.3; @entity3988 , 5.7 +/- 0.7 vs. 4.2 +/- 0.7 ml/min per 100 ml: all not significant), although FBF responses to @entity1617 were significantly reduced by @entity7293 . In conclusion, direct NO liberation does not make a significant contribution to the vasodilation associated with first-generation CCBs in healthy @entity1 resistance vessels.

XXXX plays an insignificant role in direct vasodilator effects of @entity460 channel blockers in healthy @entity1 .

@entity1 :: ('9606', 'Species') :: ['human', 'men'] @entity3360 :: ('MESH:D009529', 'Chemical') :: ['nicardipine'] @entity3988 :: ('MESH:D004110', 'Chemical') :: ['diltiazem'] @entity1617 :: ('CHEBI:22614', 'Chemical') :: ['ACh'] @entity7293 :: ('CHEBI:28229', 'Chemical') :: ['L-NMMA'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity594 :: ('MESH:D009543', 'Chemical') :: ['nifedipine'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity842 :: (MESH:D009569,Chemical) :: ['Nitric oxide']
