Augmented natriuretic peptide-induced guanylyl cyclase activity and vasodilation in experimental hyperglycemic rats

The present study was aimed to investigate whether hyperglycemia may alter the regulation of vascular natriuretic peptide receptors (NPR). The hyperglycemia was induced in rats by the treatment with streptozotocin (50 mg/kg, i.v.). The expression of different subtypes of NPR was determined in the thoracic aorta by reverse transcriptase-polymerase chain reaction and quantitative in vitro receptor autoradiography. The isometric tension and the guanylyl cyclase activity of the isolated thoracic aorta in response to natriuretic peptides were also determined. Following the treatment with streptozotocin, the plasma concentration of atrial natriuretic peptide (ANP) was significantly increased. The expression of NPR-A was increased, while that of NPR-C was reduced. The receptor binding study demonstrated an increased maximal binding capacity of NPR, with its affinity not significantly altered. The magnitude of vasodilation and guanylyl cyclase activity in response to ANP was significantly increased. On the other hand, the vasodilator response as well as the tissue formation of cGMP in response to acetylcholine or sodium nitroprusside was significantly reduced. These results indicate that the hyperglycemia may cause an altered regulation of vascular NPR.