Effect of intravenous enkephalin administration on kallikrein-kinin system in experimental hemorrhagic shock. Evidence for activation of kallikrein-kinin system by naloxone.
The effects of enkephalin derivates with different opioid receptor subtype specificity and naloxone on cardiovascular responses and kallikrein-kinin system (KKS) were studied in anesthetized rats exposed to 30% hemorrhage. Administration of a mu-receptor agonist (DAGO) in early hemorrhage improved mean arterial blood pressure (MAP) responses to hemorrhage. This effect could be abolished by naloxone pretreatment. Moreover, a delayed MAP recovery after hemorrhage could be observed. Treatment with a delta-agonist (DADL) resulted in transient depression of MAP and heart rate (HR). Hemorrhage by itself caused only a slight activation of KKS as indicated by decreased plasma kallikreinogen concentration and reduced kallikrein inhibitor capacity after 20% blood loss. Enkephalin administration did not exert significant effects on KKS. Naloxone pretreatment, in contrast, induced prehemorrhagic activation of KKS, which was potentiated by subsequent hemorrhage. Naloxone-induced activation of KKS could be confirmed by an in vitro study. Taken together these results suggest that the KKS is not involved in MAP and HR responses to enkephalin administration during hemorrhage, whereas it might be implicated in naloxone-induced delayed posthemorrhagic MAP recovery.
Grässler
J
J
Institute of Pathological Biochemistry, Medical Academy, Carl Gustav Carus, Dresden, GDR.
Kühne
H
H
Slepuschkin
V D
VD
Zoloev
G K
GK
Scheuch
D W
DW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D006470:Hemorrhage / Q000503:physiopathology; D007275:Injections, Intravenous; D007610:Kallikreins / Q000502:physiology*; D007705:Kinins / Q000502:physiology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012771:Shock, Hemorrhagic / Q000503:physiopathology*
D004745:Enkephalins; D007705:Kinins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D007610:Kallikreins