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Nitric oxide plays an insignificant role in direct vasodilator effects of calcium channel blockers in healthy humans.

Author(s): Nakamura M, Arakawa N, Yoshida H, Naganuma Y, Nagano M, Hiramori K

Affiliation(s): Second Department of Internal Medicine, Iwate Medical University, Morioka, Japan.

Publication date & source: 2002-03, Heart Vessels., 16(3):105-10.

Publication type: Clinical Trial; Randomized Controlled Trial

Several experimental studies have suggested that the vasodilatory effects of calcium 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 nitric oxide (NO) in the human 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 men (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 (nifedipine, nicardipine, diltiazem). Subdepressor doses of CCBs [4, 8, 16, 24, and 36 (diltiazem 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: L-NMMA) was infused intra-arterially, and the FBF response to CCBs was again determined. Further, as a positive control for NO stimulation, acetylcholine (ACh) was also examined before and after L-NMMA 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 L-NMMA (FBF at maximum doses: nifedipine, 8.0 +/- 0.8 vs. 7.3 +/- 0.7; nicardipine, 7.3 +/- 1.5 vs. 6.5 +/- 1.3; diltiazem, 5.7 +/- 0.7 vs. 4.2 +/- 0.7 ml/min per 100 ml: all not significant), although FBF responses to ACh were significantly reduced by L-NMMA. In conclusion, direct NO liberation does not make a significant contribution to the vasodilation associated with first-generation CCBs in healthy human resistance vessels.

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