Vascular reactivity stimulated by TMA and TMAO: Are perivascular adipose tissue and endothelium involved?

Autor(es)

Restini, Carolina Baraldi A. ^{[1, 2]} ; Fink, Gregory D. ^[1] ; Watts, Stephanie W. ^[1]

Afiliação do(s) autor(es)

^[1] Michigan State Univ, Dept Pharmacol & Toxicol, 44575 Garfield Rd, Bldg UC4, E Lansing, MI 48824 - USA

^[2] Michigan State Univ, Coll Osteopath Med, 44575 Garfield Rd, Bldg UC4, Clinton Township, MI 48038 - USA

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOLOGICAL RESEARCH; v. 163, JAN 2021.
• Citações Web of Science: 0

Resumo

Trimethylamine (TMA), formed by intestinal microbiota, and its Flavin-Monooxygenase 3 (FMO3) product Trimethylamine-N-Oxide (TMAO), are potential modulators of host cardiometabolic phenotypes. High circulating levels of TMAO are associated with increased risk for cardiovascular diseases. We hypothesized that TMA/TMAO could directly change the vascular tone. Perivascular adipose tissue (PVAT) helps to regulate vascular homeostasis and may also possess FMO3. Thoracic aorta with(+) or without(-) PVAT, also + or - the endothelium (E), of male Sprague Dawley rats were isolated for measurement of isometric tone in response to TMA/TMAO (1nM-0.5 M). Immunohistochemistry (IHC) studies were done to identify the presence of FMO3. TMA and TMAO elicited concentration-dependent arterial contraction. However, at a maximally achievable concentration (0.2 M), contraction stimulated by TMA was of a greater magnitude (141.5 +/- 16% of maximum phenylephrine contraction) than that elicited by TMAO (19.1 +/- 4.03%) with PVAT and endothelium intact. When PVAT was preserved, TMAO-induced contraction was extensively reduced the presence (19.1 +/- 4.03%) versus absence of E (147.2 +/- 20.5%), indicating that the endothelium plays a protective role against TMAO-induced contraction. FMO3 enzyme was present in aortic PVAT, but the FMO3 inhibitor methimazole did not affect contraction stimulated by TMA in aorta + PVAT. However, the L-type calcium channel blocker nifedipine reduced TMA-induced contraction by similar to 50% compared to the vehicle. Though a high concentration of these compounds was needed to achieve contraction, the findings that TMA-induced contraction was independent of PVAT and E and mediated by nifedipine-sensitive calcium channels suggest metabolite-induced contraction may be physiologically important. (AU)

• Processo FAPESP: 15/25822-9 - Sistema adrenérgico funcional em tecido adiposo perivascular renal
• Beneficiário: Carolina Baraldi Araujo Restini
• Modalidade de apoio: Bolsas no Exterior - Pesquisa