Vascular alpha-adrenoceptor blockade by E. coli endotoxin in the rat

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Endotoxicology

Background:

• Escherichia coli endotoxin (ENDO) is known to diminish the pressor effects of phenylephrine.
• The precise mechanism of ENDO's interaction with vascular alpha-adrenoceptors remains to be fully elucidated.

Purpose of the Study:

• To investigate the specific involvement of vascular alpha-adrenoceptors in the action of Escherichia coli endotoxin.
• To determine if ENDO exhibits selectivity between alpha 1 and alpha 2 adrenoceptor subtypes.

Main Methods:

• Experiments were conducted using pithed rats and perfused rat kidneys.
• Dose-response curves for alpha-agonists (noradrenaline, St 587, B-HT 933) were analyzed following ENDO pretreatment.
• Intravenous injections of ENDO at doses of 10 and 100 micrograms/kg were administered.

Main Results:

• ENDO pretreatment caused a rightward shift in the dose-response curves of noradrenaline, St 587, and B-HT 933 in pithed rats.
• In perfused rat kidneys, ENDO (10 and 30 micrograms) also shifted the noradrenaline dose-response curve to the right.
• These findings indicate a blockade of vascular alpha-adrenoceptors by ENDO.

Conclusions:

• Escherichia coli endotoxin exerts a significant blocking effect on vascular alpha-adrenoceptors.
• The blocking action of ENDO on alpha-adrenoceptors appears to be non-selective, affecting both alpha 1 and alpha 2 subtypes.
• This research clarifies the role of alpha-adrenoceptors in mediating the cardiovascular effects of endotoxin.