Stroma-free hemoglobin increases blood pressure and GFR in the hypotensive rat: role of nitric oxide.
The short-term systemic and renal hemodynamic effects of two stroma-free hemoglobin (SFH) solutions, one unmodified and the other modified by cross-linking, were examined in anesthetized rats after hemorrhagic hypotension. Both forms of SFH increased mean arterial pressure (MAP) and glomerular filtration rate (GFR) to baseline (prehemorrhage) values. The increase in MAP induced by unmodified SFH was greater than the increase in MAP caused by an albumin solution isoncotic to the unmodified SFH solution. Similarly, the increase in MAP caused by the modified SFH was also substantially greater than that induced by an albumin solution of comparable oncotic pressure to the modified SFH solution. Both unmodified and modified SFH increased GFR. As with MAP, the increase in GFR induced by both SFH solutions was greater than that associated with the oncotically matched albumin solutions. In separate experiments, the effects of nitric oxide (NO) inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) on MAP after hemorrhagic hypotension and subsequent infusion of unmodified SFH or albumin were also examined. In the albumin-infused rats, L-NAME increased MAP. In marked contrast, NO inhibition with L-NAME had no further effect on MAP when infused after SFH. We conclude that both unmodified and modified SFH solutions acutely improve MAP and GFR by the combined effects of intravascular volume expansion resulting from the colloid effect of the protein and by inactivation of NO.
Thompson
A
A
Evans Memorial Department of Clinical Research, Boston University Medical Center, Massachusetts 02118.
McGarry
A E
AE
Valeri
C R
CR
Lieberthal
W
W
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects*; D001802:Blood Substitutes / Q000493:pharmacokinetics / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006454:Hemoglobins / Q000493:pharmacokinetics / Q000494:pharmacology*; D006470:Hemorrhage / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
D001802:Blood Substitutes; D006454:Hemoglobins; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D019331:NG-Nitroarginine Methyl Ester