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

Abstract 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 H -[1,2,4]oxadiazolol [4,3,-α]quinoxalin-1-one (ODQ, 10 μM), a soluble guanylate cyclase inhibitor, but not N ω -nitro- l -arginine methyl ester ( l -NAME, 100 μM), an inhibitor of NO synthase (NOS), attenuated the relaxation to isoproterenol (59±16%, P N -[2-(( p -bromocinnamyl)aminoethyl]-5-isoquinolinesulfonamide hydrochloride (H-89) (8 μM), 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.