Together, the findings support a gut microbiota-dependent component of nifedipine-mediated vascular protection that extends beyond blood pressure lowering, involving Bifidobacterium animalis subsp. lactis 420 (B420), increased inosine availability, and Adora2b signaling.
Nifedipine ameliorated gut dysbiosis in high-salt hypertensive rats.
Transplanting nifedipine-modulated microbiota improved gut barrier integrity and reduced vascular injury while only marginally lowering blood pressure.
Depleting the microbiota markedly attenuated nifedipine's vascular benefits without abolishing its blood pressure lowering.
Supplementing B420 or inosine recapitulated major vascular protective effects of nifedipine without statistically significant blood pressure changes.
In hypertensive patients, nifedipine treatment was associated with higher intestinal B420 abundance and inosine levels.
Inosine modulates macrophages in an Adora2b- and Rap1-dependent manner, with accompanying changes in cAMP and KLF4, and this ameliorates VSMC dysfunction via paracrine signaling.
Systemic Adora2b antagonism attenuated the vascular protective effects of both inosine and B420 in vivo.
The authors propose B420 and inosine as candidate adjuncts to calcium channel blocker therapy.
This study asked whether the blood vessel protection from the blood pressure drug nifedipine depends partly on gut bacteria. In rats fed a high-salt diet to cause hypertension, nifedipine corrected an imbalance in gut microbes. Transferring gut microbes from nifedipine-treated rats to other hypertensive rats improved gut barrier function and reduced vascular inflammation, oxidative stress, scarring (collagen deposition), and abnormal changes in vessel muscle cells, while barely changing blood pressure. When gut microbes were depleted, nifedipine still lowered blood pressure but its vessel protection was much weaker. The researchers traced part of this effect to a bacterium, Bifidobacterium animalis subsp. lactis 420, and a molecule called inosine. Giving either one reproduced much of nifedipine's vessel benefit without significant blood pressure changes. In a small group of hypertensive patients, nifedipine treatment was associated with more of this bacterium and higher inosine in the gut. Lab experiments suggested inosine acts on immune cells (macrophages) through a receptor called Adora2b, which then influences nearby vessel muscle cells. Blocking this receptor in animals reduced the benefits of inosine and the bacterium. This research suggests that some of the vascular benefits of nifedipine may come from its effects on gut microbes, not just from lowering blood pressure. The authors suggest the bacterium and inosine as possible add-on treatments, but the work is mostly in rats and cells, with only a small pilot human study showing association, so it does not yet show benefit in people.
Ren X, Yan X, Tang P, Jin J, Qin Z, Zhang Y, et al.. (2026). Nifedipine-modulated gut microbiota attenuates hypertensive vascular injury through Bifidobacterium-associated inosine-Adora2b signaling.. Pharmacological research. https://doi.org/10.1016/j.phrs.2026.109684