Influence of morphine or capsaicin pretreatment on rat gastric microcirculatory response to PAF.
Capsaicin pretreatment, which destroys primary sensory afferent neurons, or morphine, which can inhibit peripheral sensory neurons, augments gastric damage induced by platelet-activating factor (PAF). The concurrent effects of such treatments on the changes in gastric mucosal blood flow (GMBF), as estimated by hydrogen gas clearance, and in systemic arterial blood pressure (BP) have now been determined in anesthetized rats. Intravenous infusion of PAF (25 and 50 ng.kg-1.min-1 for 30 min) induced dose-related histologically assessed mucosal damage, which was significantly potentiated by neonatal capsaicin pretreatment. Capsaicin pretreatment did not affect resting BP or GMBF or the fall in BP induced by PAF but did significantly potentiate the PAF-induced reduction in GMBF. Likewise, morphine (1.5 mg/kg iv) did not affect resting BP or GMBF or the fall in BP but did enhance the reduction in GMBF and potentiated the mucosal damage after PAF infusion; both of these effects were abolished by the opioid-antagonist naloxone (1 mg/kg iv). These findings indicate that the deleterious gastric microcirculatory changes induced by PAF are enhanced by functional ablation of sensory afferent neurons and by morphine, which may act on these neurons; these effects may therefore underlie the potentiation of gastric damage. Such local sensory neurons thus appear to be involved in the regulation of local protective microvascular responses to noxious challenge.
Pique
J M
JM
Gastrointestinal Unit, Hospital Clinic, Barcelona, Spain.
Esplugues
J V
JV
Whittle
B J
BJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects
D010972:Platelet Activating Factor; D009270:Naloxone; D009020:Morphine; D002211:Capsaicin