Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats

1 Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an i mportant role in vasodilatation and blood pressure regulation. We investiga ted the effects of high salt intake on the nitric oxide (NO)-cyclic GMP sig nal transduction pathway regulating relaxation in aortas of spontaneously h ypertensive rats (SHR). 2 Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a nor mal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks. 3 In aortic rings from SHR, endothelium-dependent relaxations in response t o acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A2 3187 were significantly impaired by the high salt intake. The endothelium-i ndependent relaxations in response to sodium nitroprusside (SNP) and nitrog lycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchang ed. On the other hand, high salt diet had no significant effects on the rel axations of aortic rings from WKY. 4 In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SN P was decreased by the high salt intake. 5 Western blot analysis showed that the protein level of endothelial NO syn thase (eNOS) was slightly increased, whereas that of soluble guanylate cycl ase (sGC) was dramatically reduced by the high salt intake. 6 These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which le ads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not th e eNOS/NO pathway.