Spironolactone

Spironolactone is an aldosterone antagonist that acts on the aldosterone mineralocorticoid receptor (IC₅₀=24 nM) and androgen receptor (IC₅₀=77 nM), promotes podocyte autophagy and regulates pain. Spironolactone improves hypertension-related vascular hypertrophy and remodeling by reducing angiotensin II (Ang II)-induced inflammation, reduces aldosterone-induced vascular and soft tissue calcification through PIT1-dependent signaling, and alleviates vascular dysfunction in type II diabetic mice by reducing oxidative stress and restoring NO/GC signaling; at low concentrations, it and its metabolites can interfere with aldosterone biosynthesis in the adrenal cortex and inhibit voltage-dependent Ca²⁺ channels to exert antihypertensive effects^{[1][2][3][4][5][6][7][8][9][10]}. In Vitro:Spironolactone significantly inhibits Ang II-mediated ERK and AKT phosphorylation in A7r5 cells without affecting EGFR phosphorylation^[1].
Spironolactone increases PIT1 expression in human aortic smooth muscle cells in a dose-dependent manner and reverses the effects of aldosterone^[2].
Spironolactone (0, 100 nM, 1 μM, 10 μM, 30 min) inhibits Ang II-induced inflammation^[5].
Spironolactone increases the expression of podocyte-specific markers WT1 and NPHS2 and autophagy markers Beclin1 and LC3B, promoting cell autophagy^[10]. In Vivo:Spironolactone blocks aldosterone (ALDO) and restores vascular remodeling caused by long-term enhancement of the renin-angiotensin system (RAS)^[1].
Spironolactone (80 mg/L, p.o.) extends the lifespan of mesothelin mutant mice and reduces aldosterone-induced vascular and soft tissue calcification^[2].
Spironolactone (10-80 mg/mL, subcutaneous injection) increases pain behavior in a dose-dependent manner in Male Swiss albino mice thermal and electrical pain models, but reduces inflammatory visceral pain caused by intraperitoneal acetic acid and chemical pain caused by plantar capsaicin^[3].
Spironolactone (50 mg/kg, once a day for 6 weeks, oral administration) can reduce diabetes-related vascular oxidative stress and prevent vascular dysfunction by increasing the expression of antioxidant enzymes and soluble guanidyl cyclase (sGC)^[4].
Spironolactone (40 mg/kg, daily, 8 weeks, i.g.) reduces urinary albumin excretion, blood lipids and fasting blood glucose levels, alleviates renal damage, promotes autophagy and reduces podocyte loss^[10].