Effects of nitric oxide synthase inhibition on blood flow and survival in experimental skin flaps.
The aim of the present study was to examine the effect of the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME) on skin and flap blood flow, NOS activity and flap survival in an ischaemic dorsal flap model in the rat. Fifty-four rats were used in the study. l-NAME or the inactive enantiomere d-NAME was given intravenously either pre-, per- and postoperatively or only postoperatively. Controls received saline treatment. Blood pressure and skin and flap blood flow were monitored. NOS activity was measured in intact skin before and after l-NAME and d-NAME infusion and in flap tissue 48h postoperatively. Forty-eight hours postoperatively flap survival was determined in all rats. l-NAME treatment caused: (1) a marked attenuation of constitutive Ca(2+) dependent NOS activity in intact skin (p<0.001), (2) an increase in blood pressure (p<0.05), (3) a decrease in blood flow in intact skin and in skin flaps (p<0.05), and (4) a decrease in flap survival (p<0.05). In saline and d-NAME treated animals no change in blood pressure, blood flow or NOS activity in intact skin was noted. In conclusion this study shows that l-NAME attenuates constitutive Ca(2+) dependent NOS activity in intact skin, decreases skin and flap blood flow and decreases the survival of skin flaps. These results indicate that constitutive nitric oxide synthase is important for basal blood flow in skin and flap tissue and for the survival of skin flaps.
Gribbe
Orjan
O
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. orjan.gribbe@ki.se <orjan.gribbe@ki.se>
Samuelson
U E
UE
Wiklund
N P
NP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000201:enzymology; D016038:Skin Transplantation; D013524:Surgical Flaps / Q000098:blood supply*
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester