Local attenuation of systemically mediated splanchnic vasoconstriction during shock due to cholera.
Hypovolemic shock, most often due to hemorrhage, is typically associated with intense splanchnic vasoconstriction. This can be severe enough to impair the functional and structural integrity of the gastrointestinal tract. Paradoxically, with cholera the structure of the gastrointestinal tract is preserved, and the intestine continues to secrete fluid delivered to it in the circulating blood in spite of severe hypovolemic shock. This suggests that splanchnic blood flow is maintained at higher levels in hypovolemic shock due to cholera than in hypovolemic shock due to hemorrhage. Our hypothesis is that cholera toxin in the intestinal lumen activates local mechanisms that attenuate systemically mediated splanchnic vasoconstriction. Blood flow to an isolated ileal segment in situ in the anesthetized rabbit was measured continuously (ultrasound transit-time volume flow probe) for 5 to 6 h after instillation of cholera toxin into the isolated intestinal lumen. Norepinephrine was infused selectively into the mesenteric artery supplying the segment to elicit local responses uncomplicated by compensatory changes secondary to systemic effects of norepinephrine. Baseline vascular conductance increased gradually and became significantly greater in cholera toxin experiments than in vehicle experiments 5 h after treatment (P < 0.035). Animals treated with cholera toxin were less responsive to norepinephrine than vehicle treated animals were (P < 0.05) and became more so over time (P < 0.001). Our conclusion is that cholera toxin activates local mechanisms that attenuate systemically mediated splanchnic vasoconstriction, at least in part by reducing vascular responsiveness to a systemic vasoconstrictor, norepinephrine.
Huang
A H
AH
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA.
Liu
X W
XW
Leitch
G J
GJ
D000818:Animals; D002771:Cholera / Q000150:complications* / Q000503:physiopathology*; D002772:Cholera Toxin / Q000633:toxicity; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D012769:Shock / Q000209:etiology* / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D002772:Cholera Toxin; D009638:Norepinephrine