Centrally mediated hypotensive effect of E coli endotoxin in the anesthetized cat

E coli endotoxin, 1 mg/kg, injected intravenously in cats anesthetized with alpha chloralose caused an initial transient rise followed by a prolonged decrease in systemic blood pressure. The renal blood flow decreased gradually while the nictitating membrane contracted. Calculated renal vascular resistance significantly decreased 10 min after intravenous injection of the endotoxin. E coli endotoxin injected into the cisterna magna (50 micrograms/kg), and the nucleus tractus solitarius (2.5 micrograms/kg) produced an abrupt and persistent fall in the systemic blood pressure, the heart rate, the renal blood flow, and the calculated values for the renal vascular resistance. The pressor response to carotid sinus hypotension (carotid occlusion) was reduced after intracisternal and intravenous injection of E coli endotoxin. The prolonged hypotensive effects caused by the intravenous and intracisternal administration of E coli endotoxin and the reduction of the pressor response to carotid occlusion were abolished by pretreatment with phentolamine (500 micrograms/kg) intracisternally, whereas the initial increase of the blood pressure and transient contraction of the nictitating membrane remained. In conclusion, the hypotensive effect of E coli endotoxin may be mediated by a central autonomic blood pressure regulatory circuit. The endotoxin activates central alpha-adrenergic receptors that are components of a brain stem inhibitory pathway which participate in the baroreflex pressor response. This central mechanism together with the peripheral actions of endotoxin would yield the complex pathophysiological responses seen in endotoxin shock.