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

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

doi:10.3389/fphys.2022.998362

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

Front Physiol. 2022 Sep 29:13:998362. doi: 10.3389/fphys.2022.998362. eCollection 2022.

Authors

Patrizia Dardi¹, Rosangela Aparecida Dos Santos-Eichler², Sarah de Oliveira³, Marco Aurélio Ramirez Vinolo³, Niels Olsen Saraiva Câmara⁴, Luciana Venturini Rossoni¹

Affiliations

¹ Laboratory of Vascular Physiology, Institute of Biomedical Science, Department of Physiology and Biophysics, University of Sao Paulo, Sao Paulo, Brazil.
² Laboratory of Cellular Communication, Institute of Biomedical Science, Department of Pharmacology, University of Sao Paulo, Sao Paulo, Brazil.
³ Laboratory of Immunoinflammation, Institute of Biology, Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, Campinas, Brazil.
⁴ Laboratory of Transplantation Immunobiology, Institute of Biomedical Science, Department of Immunology, University of Sao Paulo, Sao Paulo, Brazil.

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.

Keywords: SCFAs-sensing receptors; butyrate; hypertension; resistance arteries; short-chain fatty acids; vascular remodeling.