Endogenous nitric oxide as a modulator of rabbit skeletal muscle microcirculation in vivo.
1. Intravital microscopy of rabbit tenuissimus muscle microvasculature was used for in vivo studies of the role of endogenous nitric oxide (NO) in local vascular control. Derivatives of arginine were applied topically in order to modulate the formation of NO from L-arginine. 2. L-NG-monomethylarginine (L-NMMA) (10-100 microM), but not D-NG-monomethylarginine (D-NMMA), dose-dependently reduced microvascular diameters. The vasoconstriction induced by L-NMMA (100 microM) was prevented by pretreatment with L-arginine (1 mM) but not with D-arginine (1 mM). Intravenous infusions of L-arginine (300 mg kg-1) reversed the effect of L-NMMA (100 microM). L-Arginine or D-arginine applied topically at 1 mM per se had no effect on microvascular diameters. 3. Vasodilatation by acetylcholine (0.03-3 microM) was significantly inhibited by L-NMMA (100 microM), whereas vasodilatation by adenosine (0.1-100 microM) or sodium nitroprusside (100 nM) was not affected. 4. The hyperaemic response after tenuissimus muscle contractions induced by motor nerve stimulation was unaffected by the presence of L-NMMA (100 microM). 5. Aggregates of platelets and white blood cells were seen in venules during superfusion with L-NMMA (100 microM), but not with D-NMMA (100 microM). 6. Our results suggest that endogenous NO formed from L-arginine is a modulator of microvascular tone and platelet and white cell-vessel wall interaction in vivo. Nitric oxide does not, however, appear to play a role in the mediation of functional hyperaemia in this tissue.
Persson
M G
MG
Dept. of Physiology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Gustafsson
L E
LE
Wiklund
N P
NP
Hedqvist
P
P
Moncada
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009046:Motor Neurons / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009132:Muscles / Q000098:blood supply*; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000241:Adenosine; D000109:Acetylcholine