Resistin Mediates Sex-Dependent Effects of Perivascular Adipose Tissue on Vascular Function in the Shrsp

• Published in: Scientific reports Vol. 9; no. 1; p. 6897
• Main Authors: Small, Heather Yvonne, McNeilly, Sarah, Mary, Sheon, Sheikh, Adam Marcus, Delles, Christian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-05-2019; Nature Publishing Group
• Subjects: 14/63; 692/308/1426; 692/4019/592/75/243; 82/80; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Arteries; Cromakalim - metabolism; Female; Females; Gene Expression Regulation; Humanities and Social Sciences; Hypertension; Hypertension - metabolism; Hypertension - pathology; Hypertension - physiopathology; Male; Mesenteric Arteries - physiopathology; multidisciplinary; Rats; Rats, Inbred SHR; Resistin - metabolism; Rodents; Science; Science (multidisciplinary); Sex; Sex Characteristics; Vasoactive agents; Vasodilation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-43326-z

Premenopausal women are relatively protected from developing hypertension compared to men. Perivascular adipose tissue (PVAT) has been shown to mediate vasoactive effects; however, a sex-dependent difference in PVAT function in the setting of hypertension has not yet been explored. We investigated the effect of PVAT on resistance vessel biology in male and female 16 week old stroke prone spontaneously hypertensive rats (SHRSP). This preclinical model of hypertension exhibits a sex-dependent difference in the development of hypertension similar to humans. Wire myography was used to assess vascular function in third-order mesenteric arteries. K
ATP
channel-mediated vasorelaxation by cromakalim was significantly impaired in vessels from SHRSP males + PVAT relative to females (
maximum relaxation: male
 + 
PVAT 46.9
 ± 
3.9% vs. female
 + 
PVAT 97.3
 ± 
2.7%
). A cross-over study assessing the function of male PVAT on female vessels confirmed the reduced vasorelaxation response to cromakalim associated with male PVAT (
maximum relaxation: female
 + 
PVAT
female
90.6
 ± 
1.4% vs. female
 + 
PVAT
male
65.8
 ± 
3.5%
). In order to explore the sex-dependent differences in PVAT at a molecular level, an adipokine array and subsequent western blot validation identified resistin expression to be increased approximately 2-fold in PVAT from male SHRSP vessels. Further wire myography experiments showed that pre-incubation with resistin (40 ng/ml) significantly impaired the ability of female + PVAT vessels to relax in response to cromakalim (
maximum relaxation: female
 + 
PVAT 97.3
 ± 
0.9% vs. female
 + 
PVAT
 + 
resistin
[40ng/ml]
36.8
 ± 
2.3%
). These findings indicate a novel role for resistin in mediating sex-dependent vascular function in hypertension through a K
ATP
channel-mediated mechanism.