High salt diet modulates cAMP- and nitric oxide-mediated relaxation responses to isoproterenol in the rat aorta.

This study tested the hypothesis that nitric oxide (NO) production contributes to relaxation induced by 3',5'-cyclic adenylate monophosphate (cAMP)-elevating agents and that high salt diet impairs this mechanism of relaxation. Relaxation response to isoproterenol but not sodium nitroprusside, a NO donor, was reduced in the thoracic aorta from rats that were placed on a high salt diet (8% NaCl; 60+/-4%, P<0.001). 1H-[1,2,4]oxadiazolol [4,3,-alpha]quinoxalin-1-one (ODQ, 10 microM), a soluble guanylate cyclase inhibitor, but not N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), an inhibitor of NO synthase (NOS), attenuated the relaxation to isoproterenol (59+/-16%, P<0.01). High salt diet also impaired the relaxation responses to forskolin, an activator of adenylate cyclase, or 8-Bromo-cAMP (8-Br-cAMP). (N-[2-((p-bromocinnamyl)aminoethyl]-5-isoquinolinesulfonamide hydrochloride (H-89) (8 microM), an inhibitor of cAMP-dependent protein kinase, did not affect the relaxation produced by isoproterenol. These data suggest that high salt diet impairs relaxation response to isoproterenol by a dual mechanism involving diminished NO/NOS pathway linked to cGMP pathway and diminished cAMP pathway that is independent of protein kinase A.