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 flow motion (rSWFM, 1-3 cycles per minute) in skeletal muscle of anesthetized ra ts was related to local changes of arterial pressure and microcirculatory b lood 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 (S NP), the partly NO-dependent metabolite adenosine (ADO), the NO-synthase in hibitor N-G-nitro-L-arginine methyl ester (L-NAME), and the mixed endotheli n receptor blocker bosentan (BOS) were analyzed. MBF and rSWFM were assesse d by laser Doppler flowmetry. rSWFM appeared in 7 out of 14 preparations af ter ADO (200 mu g/kg/min), but not after SNP (100 mu g/kg/min), L-NAME (30 mg/kg iv), and BOS (10 mg/kg iv). Its occurrence was associated with a sign ificant decrease in arterial pressure to 50 +/- 3% (mean +/- SEM) of the ba seline, provided that MBF was not enhanced. When given after induction of r SWFM by a 25% hemorrhage, SNP (50 mu g/kg/min) totally abolished rSWFM and ADO (100 mu g/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 af fected 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 negativ e correlation to changes in both MAP and MBF (R-2 = 0.61, multiple regressi on) 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. (C) 1999 Academic Press.