Submitted on June 22, 2004
Accepted on November 3, 2004
20-HETE Mediated Vasoconstriction by Hemoglobin-O2-Carrier in Sprague Dawley but not Wistar Rats
Andrew D Baines1* and Patrick Ho1
1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: andrew.baines{at}utoronto.ca.
Hypothetically either decreased NO or increased O2 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 O2-affinity into isoflurane anesthetized Wistar (W) and Sprague Dawley (SD) rats after exchanging 20% of their blood with Ringer's lactate. For comparison we infused an equal amount of bovine serum albumin (BSA) or BSA with L-NAME (BSA+NAME). Tm-Hb increased BP and renal vascular resistance (RVR) equally in W and SD. Renal blood flow (RBF, Doppler ultrasound) decreased. BSA decreased RVR and raised GFR. 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. Arterial O2-content with BSA was lower than with Tm-Hb but O2-delivery was 60% higher with BSA because of higher RBF. BSA raised pO2 (Oxylite) in cortex and medulla and reduced RVR. Tm-Hb decreased pO2 and increased RVR. Switching rats from breathing air to 100% O2 raised intrarenal pO2 2-3 fold and increased BP and RVR. HET0016 did not alter hyperoxic responses. Conclusion: 20-HETE contributes to vasoconstriction by Tm-Hb in SD but not in W and increased 20-HETE activity results primarily from decreased NO.
