Excitatory action of lead on rat sympathetic preganglionic neurons in vitro and in vivo.
Lead exposure elicited an increase in blood pressure and was considered to be a cardiovascular risk factor. The involvements of sympathetic nervous system and circulating catecholamines have been implicated in lead-induced hypertension. This study examined the effects of PbCl(2) on sympathetic preganglionic neurons (SPNs) in vitro and in vivo. In vitro electrophysiological study showed that superfusion of a low concentration (5 microM) of PbCl(2), which had no effects on membrane potential and spontaneous discharge rate, enhanced excitatory postsynaptic potentials (EPSPs) in some of the SPNs examined but inhibited inhibitory postsynaptic potentials (IPSPs) in other SPNs tested. A higher concentration (50 microM) of PbCl(2) inhibited both EPSPs and IPSPs in all SPNs examined. In vivo study showed that intrathecal injection of PbCl(2) (10 and 100 nmol) via an implanted cannula to the T7-T9 segments of urethane-anesthetized rats increased both the heart rate and mean arterial pressure. The pressor and tachycardic responses of intrathecal PbCl(2) (100 nmol) were attenuated by pretreatment with intravenous administration of hexamethonium (10 mg/kg) or intrathecal AP-5 (DL-2-amino-5-phosphonovaleric acid, 100 nmol), but were not significantly antagonized by prior intrathecal administration of CNQX (6-cyano-7-nitroquinoxaline-2,3-dione, 100 nmol). Taken together, these results demonstrated that lead may exert a stimulatory effect on SPNs, which may result from the enhancement of EPSPs and inhibition of IPSPs by low concentrations of lead.
Lai
Chih Chia
CC
Department of Pharmacology, Tzu Chi University, 701, Section 3, Chung-Yang Road, 970, Hualien, Taiwan. cclai@mail.tcu.edu.tw
Lin
Hsun Hsun
HH
Chen
Chun Wen
CW
Chen
Szu Hsuan
SH
Chiu
Ted H
TH
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D005724:Ganglia / Q000166:cytology / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects*
D007854:Lead; D018738:Hexamethonium; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate