Postshock mesenteric lymph drainage ameliorates vascular reactivity and calcium sensitivity through RhoA.
BACKGROUND
Vascular hyporeactivity plays an important role in the pathogenesis of severe shock. Previous studies have shown that postshock mesenteric lymph (PSML) blockage ameliorates the vascular reactivity and calcium sensitivity, and RhoA is involved in the regulation of vascular reactivity after hemorrhagic shock. Therefore, the present study tested whether small GTPase RhoA mediates the improvement of the vascular reactivity and calcium sensitivity in superior mesenteric artery (SMA) of rats with PSML drainage.


METHODS
The hemorrhagic shock model (blood pressure to 40 ± 2 mm Hg) was established, and PSML was drained from immediate hypotension for 3 h, after which SMA was isolated, and the vascular reactivity and calcium sensitivity were tested in the presence of RhoA agonist (U-46619) or inhibitor (C3 transferase). The protein expressions of small GTPase RhoA and phospho-RhoA were also examined in SMA.


RESULTS
The hemorrhagic shock resulted in a significant decrease in the SMA reactivity and calcium sensitivity, which was enhanced by the application of U-46619 to the SMA. In contrast, the PSML drainage ameliorated the deleterious effect of the hemorrhagic shock on the SMA. This beneficial effect of the PSML drainage was abolished by C3 transferase. Western blotting revealed that the expressions of the RhoA and phospho-RhoA in SMA tissue obtained from the shock group were significantly decreased, and the PSML drainage markedly enhanced these protein expressions.


CONCLUSIONS
RhoA is an important contributor to the PSML drainage-induced amelioration of the vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.
Institute of Microcirculation, Hebei North University, Zhangjiakou, Hebei, People's Republic of China.
Zigang
Z
Zhao
Yonghua
Y
Si
Yuping
Y
Zhang
Shuting
S
Du
Limin
L
Zhang
Chunyu
C
Niu
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D036002:ADP Ribose Transferases / Q000494:pharmacology; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004322:Drainage; D008196:Lymph / Q000502:physiology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000503:physiopathology*; D009219:Myosin-Light-Chain Kinase / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology*
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D009219:Myosin-Light-Chain Kinase; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein; D002118:Calcium
Calcium sensitivity; Drainage; Hemorrhagic shock; Mesenteric lymph; RhoA; Vascular reactivity