Reduced intestinal butyrate availability is associated with the vascular remodeling in resistance arteries of hypertensive rats

Author(s)

Dardi, Patrizia ; Dos Santos-Eichler, Rosangela Aparecida ; de Oliveira, Sarah ; Ramirez Vinolo, Marco Aurelio ; Saraiva Camara, Niels Olsen ; Rossoni, Luciana Venturini

• Document type: Journal article
• Source: FRONTIERS IN PHYSIOLOGY; v. 13, p. 12-pg., 2022-09-29.

Abstract

During hypertension an unbalance of short-chain fatty acids (SCFAs) production by intestinal bacteria is described. However, no data evaluate the association of SCFAs and vascular remodeling in hypertension, which is an important hallmark of this disease. Thus, the present study aims to evaluate the correlations between SCFAs availability and the resistance arteries remodeling in hypertension, as well as to identify the possible pathway by which the SCFAs could exert a structural and mechanical influence. Hence, male spontaneously hypertensive rats (SHR) and normotensive Wistar rats had blood pressure measured by tail-cuff plethysmography; fecal SCFAs content assessed by gas chromatography; gene expression of SCFAs-transporters in gut epithelium and SCFAs-sensing receptors on mesenteric resistance arteries (MRA) quantified by PCR; and MRA structural and mechanical parameters analyzed by pressure myograph. Reduced butyrate fecal content was found in SHR, with no changes in propionate and acetate, as well as decreased mRNA levels of SCFAs-transporters (MCT1, MCT4, and SMCT1) in the intestinal epithelium. In addition, lower gene expression of SCFAs-sensing receptors (GPR41, GPR43, and GPR109a, but not Olfr78) was identified in MRAs of SHR, which also shows inward eutrophic remodeling with stiffness. Butyrate content presented a negative correlation with systolic blood pressure and with the structural alterations found on MRAs, while a positive correlation between butyrate content and mechanical parameters was detected. Altogether the present study suggests that lower butyrate content due to ineffective SCFA bioavailability, associated with lower SCFAs-sensing receptors expression, could favor MRA remodeling, increasing peripheral vascular resistance and worsening hypertension prognosis. (AU)

• FAPESP's process: 19/08026-5 - Adaptations on perivascular innervation and remodeling in resistance arteries of DOCA-salt hypertension model: the role of endogenous ouabain
• Grantee: Luciana Venturini Rossoni
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/10381-5 - Study of the effect of cross-fostering on intestinal changes that influence vascular remodeling and the development of Arterial Hypertension
• Grantee: Patrizia Dardi
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation
• Grantee: Marco Aurélio Ramirez Vinolo
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2