Study on the participation and effects of hydrogen sulfide (H2S) on the in vitro vasomotor response of mouse mesenteric artery

• Grant number: 19/14051-2
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2020 - August 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Marcelo Nicolas Muscara
• Grantee: Marcelo Nicolas Muscara
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Soraia Katia Pereira Costa

Abstract

In view of the relevance of cardiovascular diseases in public health, the development of new therapeutic strategies is a high-priority issue. Studies carried out over the last decade show the participation of hydrogen sulphide (H2S) in several physiological systems, including the cardiovascular system. In blood vessels, H2S can act on both smooth muscle cells and endothelial cells resulting, in most cases, in vasodilation. However, the effects and the molecular mechanisms involved greatly depend on the studied vascular bed and on the type of H2S donor used. Regarding the type of blood vessel, the study of the response of resistance vessels (such as the mesenteric bed arteries) is certainly of fundamental relevance in order to propose new therapies intended for the control of hypertension. Regarding the type of H2S donor, several studies in the literature confirm that the kinetic characteristics of H2S release (e.g., spontaneous vs. slow release) or the specific target of the donor (e.g., mitochondria) result in a wide range of heterogeneous responses. In this way, the present project aims to study the in vitro vasomotor response of mouse mesenteric artery rings to spontaneous (such as NaHS), slow release (like compound GYY4137) or selective mitochondrial H2S donors (such as compounds AP39 and AP123), as well as the importance of endogenous H2S. These responses will be studied using a force myograph, by evaluating the responses to different H2S donors or inhibitors of endogenous H2S synthesis. The mechanisms of action involved will be studied pharmacologically using ion channel blockers (mainly for K+ channels) and enzymatic inhibitors (NOS and soluble guanylate cyclase), considering that these targets mediate the H2S responses in other biological systems. Complementarily, biochemical analysis (such as protein and gene expression, measurement of enzymatic activities and content of second messengers) will be performed in order to elucidate and/or confirm the molecular mechanisms involved. (AU)