Alteration of the soluble guanylate cyclase system in the vascular wall oflead-induced hypertension in rats

Low-level lead exposure is a known cause of hypertension that has been asso ciated with increased reactive oxygen species activity and endothelial-depe ndent vasorelaxation impairment. The effect of lead exposure on the vascula r nitric oxide (NO)/cyclic guanocine monophosphate (cGMP) system was analyz ed. Wistar rats were exposed to 5 ppm lead acetate in the drinking water du ring 30 d. Mean arterial BP increased significantly in the lead-treated rat s. Relaxation to both acetylcholine and sodium nitroprusside (SNP) was redu ced in lead-treated rats: however. the vascular wall of lead-administered r ats showed an increased expression of endothelial NO synthase. The expressi on of both subunits (alpha (1) and beta (1)) of soluble guanylate cyclase ( sGC) and the cGMP accumulated in the vascular wall were decreased in lead-t reated rats. Cotreatment of lead with vitamin C (3 mmol/L) prevented the in crease on mean arterial BP. improved the relaxation to both acetylcholine a nd sodium nitroprusside, and restored the normal expression of endothelial NO synthase and sGC proteins in the vascular wall. In conclusion, lead expo sure altered both the endothelium-dependent and -independent relaxing respo nse and induced a reduced expression of sGC in the vascular wall. These eff ects were abrogated with the antioxidant vitamin C. which suggests the invo lvement of reactive oxygen species in the regulation of the NO/cGMP relaxin g system in the vascular wall of lead-treated rats.