Paradoxical changes in organ blood flow after arginase infusion in the non-stressed rat.
Arginine (ARG) is the precursor of nitric oxide (NO), a potent vasodilator. Arginase (ASE) is released following hepatocellular damage, resulting in low plasma ARG levels. The effect of ASE infusion on hemodynamics was studied. Rats received a 20 min ASE or saline infusion, and systemic hemodynamics and organ blood flow were studied, at 30 and 270 min, using radiolabeled microspheres. Compared with control, ASE resulted (30 min) in 1) undetectable ARG levels; 2) higher mean arterial pressure and total peripheral resistance (both p < .05); 3) higher blood flow to the heart, kidneys, stomach, small intestine (all p < .05), and spleen (p < .001); and 4) lower vascular resistance in the heart, kidneys, stomach, and small intestine (all p < .05) and in the spleen (p < .005). At 270 min, ASE rats had similar organ blood flow and higher nitrate levels in urine and plasma (both p < .05) compared with control. We conclude that ASE reduces ARG levels with simultaneous increase in mean arterial pressure and total peripheral resistance. Higher nitrate production, suggesting higher NO formation in the presence of low ARG plasma levels, is paradoxical but could explain the higher blood flow in some organs. The increased total peripheral resistance during higher nitrate formation suggests regional differences in dependency of NO production on plasma ARG levels.
Prins
H A
HA
Department of Surgery, Free University Hospital, Amsterdam, The Netherlands.
Houdijk
A P
AP
van Lambalgen
A A
AA
Teerlink
T
T
Meijer
S
S
Thijs
L G
LG
van Leeuwen
P A
PA
D000818:Animals; D001119:Arginase / Q000494:pharmacology*; D001120:Arginine / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply; D008102:Liver Circulation; D008297:Male; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013154:Spleen / Q000098:blood supply; D014655:Vascular Resistance / Q000187:drug effects
D009566:Nitrates; D009573:Nitrites; D001120:Arginine; D001119:Arginase