20-HETE-mediated vasoconstriction by hemoglobin-O2 carrier in Sprague-Dawley but not Wistar rats.
Hypothetically either decreased nitric oxide (NO) or increased O(2) could initiate 20-HETE-mediated vasoconstriction associated with hemoglobin-based blood substitutes (HBOC). To test this hypothesis, we infused Tm-Hb, an HBOC with low O(2) affinity, into isoflurane-anesthetized Wistar (W) and Sprague-Dawley (SD) rats after exchanging 20% of their blood with Ringer lactate. For comparison we infused an equal amount of BSA or BSA with N(G)-nitro-L-arginine methyl ester (BSA + NAME). Tm-Hb increased blood pressure (BP) and renal vascular resistance (RVR) equally in W and SD rats. Renal blood flow (RBF; Doppler ultrasound) decreased. BSA decreased RVR and raised glomerular filtration rate. BSA + NAME raised BP, RVR, and GFR. HET0016, an inhibitor of 20-HETE production, blunted BP and RVR responses to Tm-Hb and BSA+NAME in SD but not W rats. Arterial O(2) content with BSA was lower than with Tm-Hb but O(2) delivery was 60% higher with BSA because of higher RBF. BSA raised Po(2) (Oxylite) in cortex and medulla and reduced RVR. Tm-Hb decreased Po(2) and increased RVR. Switching rats from breathing air to 100% O(2) raised intrarenal Po(2) two- to threefold and increased BP and RVR. HET0016 did not alter hyperoxic responses. In conclusion, 20-HETE contributes to vasoconstriction by Tm-Hb in SD but not in W rats, and increased 20-HETE activity results primarily from decreased NO.
Baines
Andrew D
AD
Department of Laboratory Medicine and Pathobiology, University of Toronto, 100 College St., Rm. 408, Toronto, Ontario M5G 1L5. andrew.baines@utoronto.ca
Ho
Patrick
P
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D001802:Blood Substitutes; D006454:Hemoglobins; D006893:Hydroxyeicosatetraenoic Acids; D009569:Nitric Oxide; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester