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1. Oxidative stress induced by reactive oxygen species (ROS) is a key mediator of haemorrhagic shock (HS)-induced vascular hyperpermeability. In the present study, curcumin, a natural anti-oxidant obtained from turmeric ( Curcuma longa), was tested against HS-induced hyperpermeability and associated ROS formation in rat mesenteric post-capillary venules in vivo and in rat lung microvascular endothelial cells (RLMEC) in vitro. 2. In rats, HS was induced by withdrawing blood to reduce mean arterial pressure to 40 mmHg for 60 min, followed by resuscitation for 60 min. To investigate vascular permeability, rats were given fluorescein isothiocyanate (FITC)–albumin (50 mg/kg, i.v.). The FITC–albumin flux was measured in mesenteric post-capillary venules by determining optical intensity intra- and extravascularly under intravital microscopy. Mitochondrial ROS formation was determined using dihydrorhodamine 123 in vivo. Parallel studies were conducted in vitro using serum collected after HS. The serum was tested on rat lung microvascular endothelial cell RLMEC monolayers. 3. In rats, HS induced a significant increase in vascular hyperpermeability and ROS formation in vivo ( P < 0.05). Treatment with curcumin (20 μmol/L) attenuated both these effects ( P < 0.05). In RLMEC in vitro, HS serum induced monolayer permeability and ROS formation. Curcumin (10 μmol/L) attenuated HS serum-induced monolayer hyperpermeability and ROS formation. Curcumin (2–100 μmol/L) scavenged 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and 1,1-diphenyl-2-picrylhydrazyl radicals in vitro, indicating its potential as a free radical scavenger. 4. The present study demonstrates that curcumin is an inhibitor of vascular hyperpermeability following HS, with its protective effects mediated through its anti-oxidant properties. [ABSTRACT FROM AUTHOR]

Hemorrhagic shock reflects low tissue perfusion that is inadequate to maintain normal metabolic functions. Often associated with this condition are impairments in cellular oxygen utilization. Rats bred for high (HCR) vs low (LCR) aerobic running capacity have greater O2 uptake and improved cardiovascular function (Gonzalez et al., J Appl Physiol 101: 1288, 2006). Hence, it was hypothesized that HCR would be more tolerant to global ischemia than LCR. To address this hypothesis, survival time to a severe controlled hemorrhage was measured. Male rats (generation 12) were catheterized and, ∼ 24 hours later, 55% of the calculated blood volume was removed during a 26 min period from conscious unrestrained animals. Rats were observed for 6 hr or until death. Contrary to our hypothesis, survival time in HCR (173 ± 55 min; n=8) did not differ (P = 0.24) from that in LCR (254 ± 52 min; n=8). Similarly, there were no differences between strains in blood pH, lactate, and base deficit values pre or post-hemorrhage. Since oxygen uptake and cardiac function are different in these rat strains, these results suggest that other mechanisms must play a more dominant role in determining survival time to hemorrhage. [ABSTRACT FROM AUTHOR]