The hydrogen sulfide donor 4-carboxyphenyl-isothiocyanate decreases blood pressure and promotes cardioprotective effect through reduction of oxidative stress and nuclear factor kappa B/matrix metalloproteinase (MMP)-2 axis in hypertension

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Pernomian, Laena ; de Mello, Marcela M. Blascke ; Parente, Juliana Montenegro ; Sanches-Lopes, Jessica M. ; Tanus-Santos, Jose Eduardo ; Parreiras e Silva, Luciana Tabajara ; Antunes-Rodrigues, Jose ; dos Santos, Raoni da Conceicao ; Elias, Lucila Leico Kagohara ; Fabro, Alexandre Todorovic ; Silva, Carlos Alberto A. ; Fazan Jr, Rubens ; de Castro, Michele Mazzaron

• Document type: Journal article
• Source: Life Sciences; v. 351, p. 14-pg., 2024-06-14.

Abstract

Aims: Our aim was to evaluate whether the hydrogen sulfide (H 2 S) donor, 4-carboxyphenyl-isothiocyanate (4CPI), exerts cardioprotective effect in the two kidney- one clip (2K -1C) rats through oxidative stress and MMP-2 activity attenuation and compare it with the classical H 2 S donor, Sodium Hydrosulfide (NaHS). Materials and methods: Renovascular hypertension (two kidneys -one clip; 2K -1C) was surgically induced in male Wistar rats. After two weeks, normotensive (2K) and hypertensive rats were intraperitoneally treated with vehicle (0.6 % dimethyl sulfoxide), NaHS (0.24 mg/Kg/day) or with 4 -CPI (0.24 mg/Kg/day), for more 4 weeks. Systolic blood pressure (SBP) was evaluated weekly by tail -cuff plethysmography. Heart function was assessed by using the Millar catheter. Cardiac hypertrophy and fibrosis were evaluated by hematoxylin and eosin, and Picrosirius Red staining, respectively. The H 2 S was analyzed using WSP-1 fluorimetry and the cardiac oxidative stress was measured by lucigenin chemiluminescence and Amplex Red. MMP-2 activity was measured by in -gel gelatin or in situ zymography assays. Nox1, gp91 phox , MMP-2 and the phospho-p65 subunit (Serine 279) nuclear factor kappa B (NF- kappa B) levels were evaluated by Western blotting. Key findings: 4 -CPI reduced blood pressure in hypertensive rats, decreased cardiac remodeling and promoted cardioprotection through the enhancement of cardiac H 2 S levels. An attenuation of oxidative stress, with inactivation of the p65-NF- kappa B/MMP-2 axis was similarly observed after NaHS or 4 -CPI treatment in 2K -1C hypertension. Significance: H 2 S is a mediator that promotes cardioprotective effects and decreases blood pressure, and 4 -CPI seems to be a good candidate to reverse the maladaptive remodeling and cardiac dysfunction in renovascular hypertension. (AU)

• FAPESP's process: 19/09174-8 - Extra- and intracellular activation of matrix metalloproteinase-2 by oxidative stress in arterial hypertension-induced vascular remodeling via extracellular matrix dependent- and independent mechanisms
• Grantee: Michele Mazzaron de Castro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/04888-5 - Gestational and neonatal treatment with antioxidant or interleukin-10 decreases maladaptive arterial remodeling and Hypertension in the adult offspring of hypertensive rats through downregulating inflammatory mediators and MMP-2 activity
• Grantee: Michele Mazzaron de Castro
• Support Opportunities: Regular Research Grants