Proton pump inhibitors and nitric oxide mechanisms in type 2 diabetes

Sertório, Jonas T.

doi:10.1007/s00125-013-3054-2

Cited by 2 publications

(2 citation statements)

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“…This includes suggesting more effective doses of esomeprazole, identifying the populations that would most benefit from using esomeprazole, or recommending alternative routes of administration for improved clinical effect. Interestingly, the oral use of proton pump inhibitors, such as esomeprazole, has been associated with decreased bioavailable nitric oxide [ 51 , 52 , 53 ]. Separate to the L-arginine/NOS pathway of nitric oxide production, a significant proportion of nitric oxide is derived from dietary nitrates and nitrites [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

“…Separate to the L-arginine/NOS pathway of nitric oxide production, a significant proportion of nitric oxide is derived from dietary nitrates and nitrites [ 54 ]. Proton pump inhibitors work to increase stomach pH, which decreases the efficiency of dietary nitric oxide production [ 51 , 52 , 53 ]. Clinical trials could avoid this deleterious effect on dietary nitric oxide production by using intraperitoneal injection, as we did in this current study.…”

Section: Discussionmentioning

confidence: 99%

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Actions of Esomeprazole on the Maternal Vasculature in Lean and Obese Pregnant Mice with Impaired Nitric Oxide Synthesis: A Model of Preeclampsia

Alwis

Binder

Mangwiro

et al. 2022

IJMS

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Preeclampsia is a devastating, multisystem disorder of pregnancy. It has no cure except delivery, which if premature can impart significant neonatal morbidity. Efforts to repurpose pregnancy-safe therapeutics for the treatment of preeclampsia have led to the assessment of the proton pump inhibitor, esomeprazole. Preclinically, esomeprazole reduced placental secretion of anti-angiogenic sFlt-1, improved endothelial dysfunction, promoted vasorelaxation, and reduced maternal hypertension in a mouse model. Our understanding of the precise mechanisms through which esomeprazole works to reduce endothelial dysfunction and enhance vasoreactivity is limited. Evidence from earlier studies suggested esomeprazole might work via the nitric oxide pathway, upregulating endothelial nitric oxide synthase (eNOS). Here, we investigated the effect of esomeprazole in a mouse model of L-NAME-induced hypertension (decreased eNOS activity). We further antagonised the model by addition of diet-induced obesity, which is relevant to both preeclampsia and the nitric oxide pathway. Esomeprazole did not decrease blood pressure in this model, nor were there any alterations in vasoreactivity or changes in foetal outcomes in lean mice. We observed similar findings in the obese mouse cohort, except esomeprazole treatment enhanced ex vivo acetylcholine-induced vasorelaxation. As acetylcholine induces nitric oxide production, these findings hint at a function for esomeprazole in the nitric oxide pathway.

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