Characterization of Perivascular Adipose Tissue (PVAT)-mediated Vasoconstriction in Isolated Arteries from Normotensive and Hypertensive Rats

Background: Although the production of both anti- and pro-contractile agents by PVAT have been described, the biological relevance of contractile substances has not yet been fully elucidated. We explored the hypothesis that vasoactive mediators released from PVAT can effectively generate vasoconstriction. Methods: Aortic rings from male and female Wistar rats (3-4 months) with (E+) and without (E-) endothelium were mounted in organ baths for functional studies. PVAT sections (~5 mm) were incubated for 30 min in 1.5 mL of physiological salt solution (PSS, 37 ºC) alone or with indomethacin, captopril, corticosterone, guanethidine, tyramine or yohimbine. Then, the PSS/PVAT was transferred to recipient vessels and the vascular tone was recorded for 30 min, followed by phenylephrine (PHE) in selected experiments. Additionally, recipient vessels were incubated with prazosin before receiving PSS/PVAT. Abdominal and mesenteric white PVAT from Wistar rats and thoracic PVAT from spontaneously hypertensive rats (SHR) were also evaluated with or without incubation of guanethidine. In separate experiments, PSS/PVAT was exposed to electric field stimulation (EFS; 20 and 30 V, 1 ms pulse, 64 Hz, 10 min). Vascular tone (in g) was expressed as mean ± SEM (n ≥ 5/group) and subjected to Student t-test or ANOVA followed by Sïdak. Results: E+ arteries incubated with PSS/PVAT were less responsive to PHE. However, this effect was preceded by a sustained contraction, which did not differ between vessels from male (0.36 ± 0.04 g) and female (0.34 ± 0.03 g) rats. PSS/PVAT-induced contraction was 3 times greater in the E-rings (1.23 ± 0.08 and 1.19 ± 0.13 g, male and female). Both abdominal and mesenteric PVAT induced a similar but less prominent effect. Indomethacin, captopril or yohimbine did not alter the effect of PSS/PVAT. Corticosterone, an inhibitor of organic cation transporter type 3 (OCT-3), enhanced PSS/PVAT-induced vasoconstriction only in female E-arteries. Despite the lack of influence of EFS, guanethidine and tyramine, drugs able to release catecholamines from vesicular storages, increased the contractile effect of PSS/PVAT by ~40 and ~250% in E+ and E-rings, regardless the sex of the donors. Similarly, guanethidine enhanced the contraction induced by abdominal and mesenteric PVAT. Moreover, prazosin vanished PSS/PVAT-induced vasoconstriction. Interestingly, the vasoconstrictive effects of the aortic PVAT from male and female SHR were ~25 and 65% lesser compared with the PVAT from normotensive rats. Conclusion: We provide functional evidence that brown and white PVAT can induce vascular contraction throughout the spontaneous and drug-sensitive extraneuronal release of an α-1 adrenergic receptor ligand. This contractile action was similar regardless of sex but was less efficient in PVAT from SHR animals, disclosing the importance of PVAT as a source of vasoconstriction in both normotensive and hypertensive rats. Understanding the role of PVAT-induced vasoconstriction in physiological and pathological conditions can add new perspectives in the management of cardiovascular diseases. CAPES 001, CNPq 405538/2021-9, 403615/2023-2 and FAPESC 733/2024. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.