[The changes in the HIF-1alpha expression during hypovolemic shock and its role in the pathogenesis of vascular hyporeactivity].
OBJECTIVE
To investigate the changes in the expression of HIF-1alpha in rat superior mesenteric artery (SMA) tissue after hypovolemic shock (HS), and its relationship with the pathogenesis of vascular hyporeactivity.


METHODS
One hundred and twelve SD rats were used in the study, and they were randomly divided into HS group (n = 56) and treatment group (n = 56, with intraperitoneal injection of 9 microg/kg oligomycin 4 h before the experiment). Arterial blood of the rats in each group were harvested at 0.0, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0 post-injury hour (PIH), respectively,with 8 rats at each time-points. Then the rats were sacrificed and superior mesenteric arteries (SMA) were harvested. Other 8 rats without any treatment served as normal controls. The changes in mRNA expression of HIF-1alpha, inducible nitric oxide synthase (iNOS) and hemeoxygenase 1 (HO-1) were determined with RT-PCR. The contraction of vascular ring of SMA to gradient concentration of norepinephrine (NE) was measured with ex vitro vascular ring tension determination method. The plasma content of carbon monoxide and nitric oxide were measured with sodium dithionite reduction method and nitrate reductase method, respectively.


RESULTS
Compared with normal controls, Vascular reactivity of SMA in HS group increased compensatorily during early stage of HS (0.0 -1.0 h), and peaked at 0.5 h. The pD2 ( - log[ NE] ) of NE decreased, but the maximal contraction (Emax) was above the normal level during 0.0 - 1.0 PIH (P < 0.01). During the middle and late shock stage, the vascular reactivity decreased gradually. The Emax decreased, pD2 increased, and the Emax was below the normal level at 4.0 PIH (P < 0.01). The increase of vascular reactivity in treatment group was partially inhibited during early stage after injury (P < 0.01). The Emax was (2.01 +/- 0. 22) g/mg at 0.5 PIH, which was obviously lower than that in HS group [(2.96 +/- 0.18) g/mg , P < 0.05]. In decompensated period of HS, the vascular reactivity was improved mildly, which exhibited obvious difference compared with that in HS group at 4.0 and 6.0 PIH (P < 0.05 or P < 0.01). HIF-1alpha mRNA expression in HS group exhibited a time-dependent increase following HS, and peaked at 4.0 PIH (P < 0.01), and the iNOS and HO-1 mRNA expression were also gradually increased, reaching the peak value at 2.0 and 4.0 PIH, respectively (P < 0.01). The plasma content of CO and NO in whole blood were gradually increased following the shock process when compared with those in normal control group, while the CO content in whole blood in treatment group maintained normal, and the plasma content of NO was obviously decreased compared with that in control group.


CONCLUSIONS
HS can elicit a dual-phase change in vascular reactivity as previously described. HIF-1alpha plays an important role in the occurrence of vascular hyporeactivity following HS.
Zhang
Yuan
Y
Department 2, Institute of Surgery Research , Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400042 , P. R. China.
Liu
Liang-ming
LM
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002248:Carbon Monoxide / Q000097:blood; D051547:Heme Oxygenase-1 / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010949:Plasma / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D051547:Heme Oxygenase-1