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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Restini, Carolina Baraldi A. [1, 2] ; Fink, Gregory D. [1] ; Watts, Stephanie W. [1]
Total Authors: 3
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: PHARMACOLOGICAL RESEARCH; v. 163, JAN 2021.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 15/25822-9 - Functional adrenergic system in renal perivascular adipose tissue (PVAT)
Grantee:Carolina Baraldi Araujo Restini
Support Opportunities: Scholarships abroad - Research