AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 3 793-R799, Copyright © 1997 by American Physiological Society

ARTICLES

Hemodynamic and renal effects of cross-linked hemoglobin infusion

A. Cases, J. M. Stulak, Z. Katusic, E. Villa and J. C. Romero
Department of Physiology and Biophysics, Mayo School of Medicine and Mayo Clinic, Rochester, Minnesota 55905, USA.

It is well known that hemoglobin binds nitric oxide (NO) and produces a pronounced vasoconstriction in isolated arteries. However, it is debatable whether such an effect takes place in whole animals, because hemoglobin also catalyzes the formation of prostaglandins from arachidonic acid. Short-term studies were performed to evaluate the effects induced by intravenous infusion of cross-linked hemoglobin (XL-Hb) on blood pressure (BP) and renal, iliac, and mesenteric flows, and on renal function in six anesthetized dogs. A similar volume-matched expansion with 6% dextran was used as a control (n = 6). Glomerular filtration rate (GFR), urinary flow, and total and fractional sodium excretion were measured before and after XL-Hb or dextran infusion to evaluate possible renal function changes. XL-Hb administration resulted in a 29% elevation in BP and a significant decrease of blood flow (30-37%) to the three vascular beds. XL-Hb did not alter GFR or sodium excretion, despite the increase in BP. In contrast, the administration of dextran did not significantly alter BP but induced a significant increase (6-13%) of blood flow in the three vascular beds. These changes were accompanied by threefold increases in urinary flow and sodium excretion without alterations in GFR. The binding effect of XL-Hb on NO was studied in isolated renal arteries in organ chambers. These in vitro studies showed that XL-Hb blunted the endothelium-mediated vasodilator response to calcium ionophore A-23187 and to acetylcholine. Our results demonstrate that XL-Hb administration is followed by hypertension, vasoconstriction, and blunted natriuresis. All these effects are compatible with the scavenging effect on NO attributed to XL-Hb.

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