Blockade of α‐adrenergic receptors in the preoptic area/anterior hypothalamus prevents lipopolysaccharide evoked hypotension

Abstract

The mechanisms responsible for endotoxic hypotension are not fully understood although previous data from this laboratory indicate that lipopolysaccharide (LPS) initially lowers arterial pressure (AP) through a central mechanism. Specifically, we showed that LPS hypotension could be prevented by inhibiting neuronal activity in the preoptic area/anterior hypothalamus (POA) with the local anesthetic lidocaine. This study tested the hypothesis that LPS lowers AP by activating α‐adrenergic receptors in the POA. Bilateral injection of the α‐adrenergic receptor antagonist phentolamine (5 ug; 1 ul) into the POA completely blocked the fall in arterial pressure evoked by LPS (1 or 15 mg/kg i.v.) in isoflurane‐anesthetized rats. Phentolamine had no effect on AP in control animals and neither LPS nor phentolamine influenced heart rate. The β‐adrenergic receptor antagonist propranolol (5 ug) was ineffective. Bilateral lidocaine injection into the nucleus tractus solitarius (NTS) also effectively prevented LPS hypotension suggesting that medullary A1/A2 noradrenergic neurons mediate the response. Importantly, phentolamine prevented the late‐developing, decompensatory phase of the hypotension induced by both low (1 mg/kg) and high (15 mg/kg) doses of LPS. These data are consistent with the hypothesis that LPS initially lowers AP by stimulating norepinephrine release in the POA.