Reversal of hemoglobin-induced vasoconstriction with sustained release of nitric oxide

Pedro Cabrales, George Han, Parimala Nacharaju, Adam J. Friedman, Joel M. Friedman

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Erythrocyte free hemoglobin (Hb) induces vasoconstriction due to nitric oxide (NO) scavenging, limiting the NO available for vascular smooth muscle. The central objective of this study was to restore NO bioavailability using long-lived circulating NO-releasing nanoparticles (NO-np) to reverse the vasoconstriction and hypertension induced by polymerized bovine Hb (PBH) NO scavenging. PBH (13 g/dl) was infused in a volume equal to 10% of the animal blood volume. Intravascular NO supplementation was provided with an infusion of NO-np (10 and 20 mg/kg body wt). This study was performed using the hamster window chamber model to concurrently access systemic and microvascular hemodynamics. Infusion of PBH increased blood pressure and induced vasoconstriction. Treatment with 10 and 20 mg/kg NO-np reduced the blood pressure and vasoconstriction induced by PBH. Moreover, the higher dose of NO-np decreased blood pressure and induced vasodilation compared with baseline, respectively. Treatment with NO-np to decrease PBH-induced vasoconstriction increased methemoglobin levels and plasma nitrite and nitrate. In conclusion, NO-np counteracted both systemic hypertension and decreased the vasoconstrictor effects of PBH infusion, improving systemic and microvascular function. Based on the observed physiological properties, NO-np has clear potential as a therapeutic agent to replenish NO in situations where NO production is impaired, insufficient, or consumed, thereby preventing vascular complications.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Vasoconstriction
Nitric Oxide
Hemoglobins
Blood Pressure
Hypertension
Methemoglobin
Vasoconstrictor Agents
Nitrites
Blood Volume
Vascular Smooth Muscle
Vasodilation
Cricetinae
Nitrates
Nanoparticles
Biological Availability
Blood Vessels
Erythrocytes
Hemodynamics

Keywords

  • Blood substitutes
  • Endothelial dysfunction
  • Gas delivery
  • Hemolysis
  • Hypertension
  • Nanotechnology
  • Transfusion medicine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Reversal of hemoglobin-induced vasoconstriction with sustained release of nitric oxide. / Cabrales, Pedro; Han, George; Nacharaju, Parimala; Friedman, Adam J.; Friedman, Joel M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 300, No. 1, 01.2011.

Research output: Contribution to journalArticle

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