Hemodynamic and renal effects of cross-linked hemoglobin infusion.
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.
Cases
A
A
Department of Physiology and Biophysics, Mayo School of Medicine and Mayo Clinic, Rochester, Minnesota 55905, USA.
Stulak
J M
JM
Katusic
Z
Z
Villa
E
E
Romero
J C
JC
D000109:Acetylcholine / Q000494:pharmacology; D000803:Angiotensin I / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D003911:Dextrans / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D007083:Iliac Artery / Q000502:physiology; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D013152:Splanchnic Circulation / Q000187:drug effects
D003911:Dextrans; D006454:Hemoglobins; D016718:Arachidonic Acid; D000001:Calcimycin; D009320:Atrial Natriuretic Factor; D000803:Angiotensin I; D012964:Sodium; D012083:Renin; D000109:Acetylcholine