Microvascular responses to E. coli endotoxin with altered adrenergic activity.
The cremaster muscle microcirculation of pentobarbital-anesthetized Wistar rats was studied using videomicroscopy. The left cremaster muscle was spread over an optical port in a bath filled with modified Krebs solution (pH 7.4, 34 degrees C). The right femoral artery was cannulated for determination of mean arterial pressure (Pm). Following control measurements of Pm and arteriolar and venular dimensions, dose-response curves of arteriolar and venular dimensions to topical norepinephrine (10(-10) M to 10(-3) M) was obtained. The rats were then administered E. coli endotoxin (6 mg/kg, iv, LD100) over a 1-hr period. The dose response curves were than repeated at intervals of 30 min. Before endotoxin the threshold dose for norepinephrine was consistently 10(-9) M or 0(-8) M. Pm decreased progressively with time postendotoxin. After endotoxin infusion, there was a gradual and progressive constriction of both arterioles and venules. The threshold dosage for norepinephrine to produce constriction of both arterioles and venules increased progressively with time. At 3 hr postendotoxin the threshold dose had increased to 10(-6) M to 10(-4) M. This is the dose that produces maximum constriction of arterioles in the preendotoxin control period. The study was terminated when the animal died or the field was obscured by petechiae. The microvessel sensitivity to norepinephrine is markedly reduced during endotoxin shock possibly due to increase in the active state of the vascular smooth muscle or to change in length of the muscle fibers or to changes in sympathetic alpha-adrenergic activity. The response was not prevented by H1 and H2 receptor blockade, but was prevented by alpha-adrenergic blockade with phentolamine.
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D008297:Male; D008785:Metiamide / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D009132:Muscles / Q000098:blood supply* / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000503:physiopathology; D014699:Venules / Q000187:drug effects
D004731:Endotoxins; D008785:Metiamide; D011738:Pyrilamine; D009638:Norepinephrine; D010646:Phentolamine