Journal of Applied Physiology
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J Appl Physiol 98: 772-779, 2005. First published November 5, 2004; doi:10.1152/japplphysiol.00638.2004
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20-HETE-mediated vasoconstriction by hemoglobin-O2 carrier in Sprague-Dawley but not Wistar rats

Andrew D. Baines and Patrick Ho

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

Submitted 22 June 2004 ; accepted in final form 3 November 2004

Hypothetically either decreased nitric oxide (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 lactate. For comparison we infused an equal amount of BSA or BSA with NG-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 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 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.

blood substitutes; kidney; nitric oxide; N{omega}-nitro-L-arginine methyl ester; autoregulation; blood pressure


Address for reprint requests and other correspondence: A. D. Baines, Dept of Laboratory Medicine and Pathobiology, Univ. of Toronto, 100 College St., Rm. 408, Toronto, Ontario M5G 1L5 (E-mail: andrew.baines{at}utoronto.ca)






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