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.
Sofola
Olusoga
O
College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
Yakubu
Momoh
M
Igbo
Imaculata
I
Newaz
Mohammad
M
Oyekan
Adebayo
A
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D017673:Sodium Chloride, Dietary; D009569:Nitric Oxide; D000242:Cyclic AMP; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester