Enhanced S -Nitroso-Albumin Formation From Inhaled NO During Ischemia/Reperfusion

Abstract

Abstract-In the present study, we investigated whether inhaled nitric oxide (NO) was transported by plasma proteins, such as S-nitroso-albumin (SNO-Alb), in the feline circulation and whether this molecule delivers NO to the periphery under conditions of stress, specifically ischemia/reperfusion (I/R). A flow probe was interposed between the femoral and superior mesenteric artery for blood flow measurements, and a branch of the superior mesenteric vein was cannulated for arterial-venous sampling. In animals breathing room air, SNO-Alb was below detection level in arterial or venous blood. NO inhalation resulted in a significant arterial-venous gradient for SNO-Alb. Concomitant with this loss of SNO-Alb across the intestinal vasculature was an increase in nitrite (NO 2 Ϫ ). However, this release of NO was not sufficient to alter intestinal blood flow. I/R during NO inhalation caused a very large increase in arterial SNO-Alb that permitted a 5-fold increase in SNO-Alb consumption and significant generation of NO 2 Ϫ within the postischemic intestinal vasculature. The increased SNO-Alb consumption was sufficient to dramatically improve intestinal blood flow. The very large burst of arterial SNO-Alb during I/R was completely blocked by the administration of superoxide dismutase, suggesting that oxidative stress contributed to the increased SNO-Alb formation. Our data suggest that inhaled NO can increase nitrosothiol production and these molecules may be a functional NO delivery system during cardiovascular disease. Key Words: S-nitroso-albumin Ⅲ oxidative stress Ⅲ postischemic vasculature I n the last 10 years, a significant development in the respiratory field has been the use of inhaled nitric oxide (NO), initially in infants with pulmonary hypertension, but more recently with adults who have respiratory distress as one manifestation of multiple-organ dysfunction syndrome. 1 Experimentally, inhaled NO has been shown to prevent lung injury from hemodialysis, 2 endotoxemia, 3 ischemia/reperfusion (I/R) injury, 4 and even lung allografts. 5 Clinically, inhaled NO is used as a local vasodilator in the pulmonary vasculature. However, because the prevailing view has been that inhaled NO is rapidly inactivated in the pulmonary capillaries by reaction with oxyhemoglobin, 6 most research in this area has been restricted to the lung. Recently, work has focused on the potential effects of inhaled NO on peripheral microvessels. Interestingly, inhaled NO has been reported to reduce systemic vascular resistance, 7 increase kidney filtration rates, 8 increase aortic cGMP levels, 9 and improve blood flow in intestine after NO synthase inhibitors. 10,11 The latter work has been extended by Cannon and colleagues 12 who reported that after blockade of forearm NO production followed by forearm exercise, NO inhalation greatly improved blood flow. Clearly, the bulk of evidence would support the view that inhaled NO can be transported to peripheral vasculatures.Although NO reacts very quickly with heme groups, thereby allowing for rap...

Cardioprotection and mitochondrial S-nitrosation: Effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia–reperfusion injury

“…Such a mechanism may underlie the cardioprotective effects of diverse agents such as SNO-MPG, NO • donors [16], and nitrite [21,50,[85][86][87]. Mitochondria were treated with GSNO or SNO-MPG at the concentrations given on the x-axis, as detailed in the methods.…”

“…While ischemic conditions (acidic pH) can favor SNO formation from nitrite [21,50], and hypoxia has been proposed to enhance complex I Snitrosation [51], it is known that typical laboratory lighting conditions can degrade SNOs. Therefore, we examined the effects of light vs. dark on the recovery of Langendorff perfused rat hearts subjected to IR injury (laboratory light spectrum shown in Figure 6B).…”

ANESTEZJOLOGIA I INTENSYWNA TERAPIA Inhaled nitric oxide effects outside the lungs – experimental and clinical evidence

“…NO inhalation resulted in a significant A-V gradient for S-nitrosoalbumin (SNO-Alb). Concomitant with this loss of SNO-Alb across the intestinal vasculature was an increase in nitrite and significantly improved intestinal blood flow [26]. In Da and colleagues' study, the combination of iNO 30 ppm and intravenous corticosteroids modifies endotoxin-induced organ damage in a piglet endotoxin model [27].…”

Chimeric SOD2/3 inhibits at the endothelial-neutrophil interface to limit vascular dysfunction in ischemia-reperfusion

“…In two series of animals (n ϭ 5), an identical protocol was completed; however, 0.5 mg of SOD2 or SOD2/3 was administered via the cannulated jugular vein after 55 min of ischemia. This dose of ϳ1 U/g body wt was chosen on the basis of previous reports that these protocols were efficacious in vivo in other inflammatory models (5,9,16,39).…”