RGD Reference Report - Mechanisms responsible for vascular hyporesponsiveness to adrenomedullin after hemorrhage: the central role of adrenomedullin binding protein-1. - Rat Genome Database

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Mechanisms responsible for vascular hyporesponsiveness to adrenomedullin after hemorrhage: the central role of adrenomedullin binding protein-1.

Authors: Wu, R  Cui, X  Dong, W  Zhou, M  Simms, HH  Wang, P 
Citation: Wu R, etal., Ann Surg. 2005 Jul;242(1):115-23.
RGD ID: 7364990
Pubmed: PMID:15973109   (View Abstract at PubMed)
PMCID: PMC1357712   (View Article at PubMed Central)

OBJECTIVE: Irreversible hypovolemia remains a major clinical problem. Preliminary studies indicate that administration of adrenomedullin and adrenomedullin binding protein-1 in combination (AM/AMBP-1) after hemorrhage, improves cardiovascular function despite the increased levels of AM. Our aim was to determine whether vascular responsiveness to AM is reduced after hemorrhage and, if so, to elucidate the possible mechanism responsible for such hyporesponsiveness. METHODS: Male rats were bled to and maintained at a mean arterial pressure of 40 mm Hg for 90 minutes. The animals were then resuscitated with 4 times the volume of shed blood with lactated Ringer's solution over 60 minutes. At 1.5 hours postresuscitation, vascular responses to AM and AMBP-1, plasma levels of AM and AMBP-1, AMBP-1 and AM receptor gene expression were measured. In additional animals, AM and AMBP-1 were administered intravenously at 15 minutes after resuscitation over 45 minutes. Serum levels of liver enzymes, lactate, creatinine, TNF-alpha, IL-6, and IL-10 were measured at 1.5 hours postresuscitation. RESULTS: AM-induced vascular relaxation decreased significantly after hemorrhage and resuscitation, which was markedly improved by AMBP-1. However, AM receptor gene expression did not change under such conditions. Hemorrhage-induced AM hyporesponsiveness was accompanied by the decreased expression and release of AMBP-1. Moreover, AM/AMBP-1 treatment down-regulated TNF-alpha and IL-6, up-regulated IL-10, and attenuated organ injury. CONCLUSIONS: The decreased AMBP-1 levels rather than alterations in AM receptors are responsible for producing AM hyporesponsiveness after hemorrhage. Thus, administration of AMBP-1 in combination with AM can be useful to reduce organ injury after severe hypovolemia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hemorrhagic Shock  ISOAdm (Rattus norvegicus)7364990; 7364990 RGD 
Hemorrhagic Shock  IEP 7364990; 7364990 RGD 
Hemorrhagic Shock  ISOCfh (Rattus norvegicus)7364990; 7364990 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adm  (adrenomedullin)
Cfh  (complement factor H)

Genes (Mus musculus)
Adm  (adrenomedullin)
Cfh  (complement component factor h)

Genes (Homo sapiens)
ADM  (adrenomedullin)
CFH  (complement factor H)


Additional Information