Dietary silica modifies the characteristics of endothelial dilation in rat aorta.
Considering the importance of nitric oxide generation in the regulation of vessel tone, reduced endothelial nitric oxide synthase (eNOS) expression in alveolar macrophages exposed to short-term silica (Si) suggests the possibility of Si-induced changes in endothelial functions. In this experimental study, the functional changes of the endothelial cells were investigated in the aortic rings of rats subjected to 50 mg Si/kg body weight in their drinking water for 8 days. Norepinephrine elicited contractility and dilation response to acetylcholine (ACh) was significantly high in the aortic rings of Si-treated group. Alteration in receptor-independent endothelial response to A23187 in the aortic rings of Si-exposed rats was less obvious, but sodium nitroprusside (SNP)-elicited dilation was reduced significantly. A23187-induced relaxation was fully eliminated with N-nitro-L-arginine methyl ester (L-NAME) pretreatment, whereas 19.24 +/- 4.36% of ACh response was L-NAME resistant and eliminated with 10-5 M tetraethylammonium (TEA). Despite a significant reduction in the share of NO, the contribution of indomethacine (IND)-sensitive relaxation to ACh response remained unchanged in Si group. As a result, our findings demonstrated that Si both modifies the characteristics of endothelial relaxants and attenuates smooth muscle cell responsiveness to NO. Si-induced reduced NO association with elevated endothelium-derived hyperpolarizing factor (EDHF) in response to ACh, together with reduced NO sensitization, might have clinical importance in cardiovascular pathology.
Oner
Gülsen
G
Department of Physiology, Medical Faculty, Akdeniz University, Antalya, Turkey. onerg@akdeniz.edu.tr
Cirrik
Selma
S
Bulbul
Mehmet
M
Yuksel
Selahattin
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001685:Biological Factors / Q000378:metabolism; D019587:Dietary Supplements; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005526:Food, Formulated; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009924:Organ Culture Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D013995:Time; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001685:Biological Factors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D019789:Tetraethylammonium; D012822:Silicon Dioxide; D019331:NG-Nitroarginine Methyl Ester