High salt intake delayed angiotensin II-induced hypertension in mice with a genetic variant of NADPH oxidase.
BACKGROUND
gp91(PHOX), a catalytic subunit of NAD(P)H oxidase, is involved in angiotensin II (Ang II)-induced superoxide (O₂⁻) generation. This study was designed to examine the hypothesis that an enhancement in O₂⁻ generation due to elevated Ang II induces salt-sensitivity, which contributes to the development of hypertension.


METHODS
Assessment of blood pressure and renal excretory responses to Ang II infusion (2.2 ng·min/g) for 2 weeks via osmotic minipump was made in knockout (KO; n = 20) mice lacking the gene for gp91(PHOX) which were fed on either normal-salt (NS; 0.04% NaCl) or high-salt (HS, 4% NaCl) diet and compared these responses with those in wild-type (WT; n = 23) mice.


RESULTS
Ang II induced increase in systolic blood pressure (SBP) was started within the 4th day in all groups except in HS fed KO mice in which SBP increased after the 10(th) day of Ang II infusion. The increases in SBP were lower in KO than WT mice at the end of 2-week infusion period. In Ang II + HS fed KO mice, the urinary excretion rate of nitrite/nitrate (U(NOx)V) markedly increased but 8-isoprostane excretion rate remained unchanged. These findings indicate that an increase in nitric oxide (NO) with a lack of O₂⁻ formation was involved in the delayed hypertension in Ang II + HS fed KO mice.


CONCLUSIONS
These data suggest that an enhanced O₂⁻ activity and its interaction with NO contribute to the early developmental phase of Ang II-induced salt-sensitive hypertension.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.173.
Haque
Mohammed Z
MZ
Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
Majid
Dewan S A
DS
D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D006973:Hypertension / Q000209:etiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013481:Superoxides / Q000378:metabolism; D013599:Systole; D014554:Urination / Q000187:drug effects
D008562:Membrane Glycoproteins; D017673:Sodium Chloride, Dietary; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D012964:Sodium; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases