Vascular hyporeactivity is an important factor in irreversible
shock, whereas
calcium desensitization is one of the mechanisms of vascular hyporeactivity, and the intestinal lymphatic pathway plays an important role in multiple organ injury after severe
hemorrhagic shock (HS). In this study, our aims were to determine the effects of mesenteric lymph on vascular reactivity during HS and the mechanisms involved. First, the in vivo pressor response was observed by
intravenous injection of
norepinephrine (3 μg/kg) at different time points after HS. We found that mesenteric lymph duct
ligation (MLDL) and mesenteric lymph drainage (MLD) enhanced the pressor response at multiple time points after
shock. Next, vascular reactivity and
calcium sensitivity in superior mesenteric artery (SMA)
vascular rings were examined using an isolated organ perfusion system. Vascular reactivity and
calcium sensitivity were higher for SMA rings from rats that had undergone HS plus MLDL or MLD that those from rats that had undergone only HS. The effects of MLDL and MLD on vascular reactivity and
calcium sensitivity were significantly increased following incubation with the
calcium sensitizer
angiotensin II and were reduced after incubation with the
calcium sensitivity inhibitor
insulin. When SMA rings from normal rats were incubated with mesenteric lymph from rats subjected to HS, lymph obtained 0 to 0.5 h after
shock enhanced vascular reactivity and
calcium sensitivity, whereas lymph obtained 1 to 3 h after
shock blunted these effects. We finally examined vascular reactivity and
calcium sensitivity in HS rats subjected to MLD at 0 to 3 h or 1 to 3 h after
shock. We found that contractile activity of SMAs in response to
norepinephrine or Ca was higher in HS rats subjected to MLD at 1 to 3 h after
shock compared with rats subjected to MLD at 0 to 3 h after
shock. These results indicate that mesenteric lymph return plays an important role in biphasic changes in vascular reactivity during HS. Even more importantly, mesenteric lymph 1 h after
shock was an important contributor to vascular hyporeactivity, and its mechanism of action was related to
calcium desensitization. Targeting lymph may therefore have therapeutic potential in the treatment of severe
shock-
induced hypotension.