Acute lead-induced vasoconstriction in the vascular beds of isolated perfused rat tails is endothelium-dependent.
Chronic lead exposure induces hypertension in humans and animals, affecting endothelial function. However, studies concerning acute cardiovascular effects are lacking. We investigated the effects of acute administration of a high concentration of lead acetate (100 microMu) on the pressor response to phenylephrine (PHE) in the tail vascular bed of male Wistar rats. Animals were anesthetized with sodium pentobarbital and heparinized. The tail artery was dissected and cannulated for drug infusion and mean perfusion pressure measurements. Endothelium and vascular smooth muscle relaxation were tested with acetylcholine (5 microg/100 microL) and sodium nitroprusside (0.1 microg/100 microL), respectively, in arteries precontracted with 0.1 microM PHE. Concentration-response curves to PHE (0.001-300 microg/100 microL) were constructed before and after perfusion for 1 h with 100 microMu lead acetate. In the presence of endothelium (E(+)), lead acetate increased maximal response (E(max)) (control: 364.4 +/- 36, Pb2(+): 480.0 +/- 27 mmHg; P < 0.05) and the sensitivity (pD(2); control: 1.98 +/- 0.07, 2.38 +/- 0.14 log mM) to PHE. In the absence of endothelium (E(-)) lead had no effect but increased baseline perfusion pressure (E(+): 79.5 +/- 2.4, E-: 118 +/- 2.2 mmHg; P < 0.05). To investigate the underlying mechanisms, this protocol was repeated after treatment with 100 microM L-NAME, 10 microM indomethacin and 1 microM tempol in the presence of lead. Lead actions on E(max) and pD(2) were abolished in the presence of indomethacin, and partially abolished with L-NAME and tempol. Results suggest that acute lead administration affects the endothelium, releasing cyclooxygenase-derived vasoconstrictors and involving reactive oxygen species.
Silveira
E A
EA
Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil. ednasilveira@terra.com.br <ednasilveira@terra.com.br>
Lizardo
J H F
JH
Souza
L P
LP
Stefanon
I
I
Vassallo
D V
DV
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*
D009942:Organometallic Compounds; D010656:Phenylephrine; C008261:lead acetate