The discovery that the endothelium is of critical importance in vascular relaxation in 1980 has led to a greater understanding of its role in vascular disease. Today it is known that endothelial dysfunction is linked to several cardiovascular disease states including atherosclerosis, diabetes mellitus and essential hypertension . The endothelium regulates vascular tone through a balanced release of both endothelium-derived relaxing factors (EDRF) and endothelium-derived contracting factors , and an impairment in one or both of these systems may be responsible for vascular dysfunction. The L-arginine derivative nitric oxide is the EDRF that has received the most attention over the past several years concerning its role in the regulation of blood pressure .The continuous basal release of nitric oxide is one of the key factors responsible for dilation of vascular smooth muscle, and this function is carried out through a guanylyl cyclase-cGMP-mediated pathway . While basal release of nitric oxide is regulated primarily by shear stress, synthesis can be enhanced by receptor-mediated agents such as acetylcholine (ACh) and bradykinin . Several studies have found defects in the EDRF system to be associated with hypertension in a variety of hypertensive models including human essential hypertension, spontaneously hypertensive rats and Dahl salt-sensitive rats. Having read all the information above and considered it carefully, our doctors recommend buying your drugs at the my canadian pharmacy.com because this is where you always get most advantageous deals on the drugs required.