Effects of subacute lead acetate administration on nitric oxide and cyclooxygenase pathways in rat isolated aortic ring.
Low level exposure to lead increases blood pressure in human and rats. In this study, we investigated the contribution of the nitric oxide (NO) and cyclooxygenase pathways of aortic rings of 28-day lead-treated and control rats, to the responsiveness to phenylephrine and acetylcholine. There were no differences in phenylephrine contractions between the two groups. N(omega)-nitro-L-Arginine-methyl ester (L-NAME), a NO synthase inhibitor, caused attenuation in contraction response to phenylephrine in the aortic rings of the lead-treated rats, while endothelium-denudation caused attenuation in those of controls. This may be due to either endothelium-derived vasoconstrictor(s) (such as reactive oxygen species or endothelins) or a source of NO in smooth muscle cells. There is a left-shift in acetylcholine relaxation response. Indomethacin incubation caused a left-shift in relaxation response to acetylcholine in controls but without any effect on lead-treated ones. Indomethacin incubation caused attenuation in contraction to phenylephrine in both groups. The relaxation response to sodium nitroprusside is not different between the two groups, suggesting that smooth muscle relaxation component is intact. However, the relaxation response to glyceryl trinitrate is impaired in aortic rings of lead-treated rats. It can be concluded that NO and cyclooxygenase pathways are altered in aortic rings of lead-treated rats, with possible involvement of endothelium-derived vasoconstrictors.
Department of Pharmacology and Toxicology, School of Pharmacy, Mashad University of Medical Sciences, Iran.
Gholamreza
G
Karimi
Ali
A
Khoshbaten
Mohammad
M
Abdollahi
Mohammad
M
Sharifzadeh
Khodadad
K
Namiranian
Ahmad Reza
AR
Dehpour
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009942:Organometallic Compounds / Q000008:administration & dosage*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D009942:Organometallic Compounds; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; C008261:lead acetate