Regular slow wave flowmotion in skeletal muscle is not determined by nitric oxide and endothelin

In a previous study we showed that the generation of regular slow wave flowmotion (rSWFM, 1-3 cycles per minute) in skeletal muscle of anesthetized rats was related to local changes of arterial pressure and microcirculatory blood flow (MBF), which suggests an involvement of pressure- or flow-induced mechanisms. The present experiments were designed to test the role of flow-dependent endothelial autacoids, such as nitric oxide (NO) and endothelin, in the generation of SWFM. The effects of NO-donor sodium nitroprusside (SNP), the partly NO-dependent metabolite adenosine (ADO), the NO-synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and the mixed endothelin receptor blocker bosentan (BOS) were analyzed. MBF and rSWFM were assessed by laser Doppler flowmetry. rSWFM appeared in 7 out of 14 preparations after ADO (200 microg/kg/min), but not after SNP (100 microg/kg/min), L-NAME (30 mg/kg iv), and BOS (10 mg/kg iv). Its occurrence was associated with a significant decrease in arterial pressure to 50 +/- 3% (mean +/- SEM) of the baseline, provided that MBF was not enhanced. When given after induction of rSWFM by a 25% hemorrhage, SNP (50 microg/kg/min) totally abolished rSWFM and ADO (100 microg/kg/min) reduced rSWFM frequency from 2.17 +/- 0.08 to 1.72 +/- 0.08 cycles per minute (cpm) (P < 0.05), whereas the frequency was not affected by the other drugs. ADO, l-NAME (30 mg/kg iv), and BOS (10 mg/kg iv) lead to changes in rSWFM amplitude which showed a drug-independent negative correlation to changes in both MAP and MBF (R(2) = 0.61, multiple regression) in the ranges of 57-176% of MAP before drug application, and 72-120% of MBF, respectively. We conclude that NO and endothelin are not involved in the generation of rSWFM. Our findings strongly suggest that the activity of rSWFM depends on a reduction of vascular wall tension and is inhibited by SNP.