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.
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 shortterm 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 receptorindependent 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 10−5M 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.
