Attenuation of arteriolar alpha 2-adrenoceptor sensitivity during endotoxemia.
It is well documented that adrenergic responses after endotoxin (ENDT) administration are greatly reduced. The hypothesis of this study is that either alpha 1- or alpha 2-receptor activity is attenuated and the other receptor type is minimally affected during ENDT shock. Reactivity of the arterioles of left cremaster muscles of male Wistar rats anesthetized with pentobarbital sodium was studied using videomicroscopy. Femoral mean arterial pressure and first-, second-, third-, and fourth-order arteriolar diameters were measured. In group I, the decreases in arteriolar diameter and half-maximal effective dose (ED50) values with increasing phenylephrine concentration (alpha 1-adrenergic receptor agonist) were similar in all four branching orders before and after ENDT. In group II, the decreases in arteriolar diameter with increasing clonidine concentrations (alpha 2-adrenergic receptor agonist) were effectively attenuated by ENDT, and ED50 values were increased above control in all four branching orders. In group III, idazoxan (alpha 2-receptor antagonist) effectively blocked the vasoconstrictor effects of clonidine but did not affect the responses to phenylephrine before or after ENDT in all four arteriolar orders. In group IV, prazosin (alpha 1-adrenergic receptor antagonist) blocked the vasoconstrictor effects of phenylephrine before and after the administration of ENDT. However, vasoconstriction due to clonidine post-ENDT even at maximal dosage (10(-3) M), was greatly attenuated in all four branching orders as in group II. It is concluded that during endotoxemia the reduced adrenergic vasoconstrictor response of cremaster muscle arterioles is the result of attenuated activity of alpha 2-adrenergic receptors with minimal if any effects on alpha 1-adrenergic receptor activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Baker
C H
CH
Department of Physiology and Biophysics, College of Medicine, University of South Florida, Tampa 33612.
Sutton
E T
ET
Price
J M
JM
Ortiz-Tweed
M
M
Nessellroth
S
S
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood; D004926:Escherichia coli; D019329:Idazoxan; D008297:Male; D009132:Muscles / Q000098:blood supply; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012772:Shock, Septic / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects
D004146:Dioxanes; D004731:Endotoxins; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D003000:Clonidine; D011224:Prazosin; D019329:Idazoxan