Abstract
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. KATP 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 + PVATfemale90.6 ± 1.4% vs. female + PVATmale65.8 ± 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 KATP channel-mediated mechanism.
Highlights
Www.nature.com/scientificreports discovered in 1991 by Soltis and Cassis who showed that Perivascular adipose tissue (PVAT) asserted anti-contractile effects on vessels through so-called ‘adventitium derived relaxing factors’ (ADRF)[10]
Altered PVAT function contributes to the sex-dependent differences in resistance vessel function in the SHRSP through exhibiting a reduced anti-contractile effect in males compared to females
Incubating female vessels with male PVAT or resistin abrogated KATP channel-mediated vasorelaxation. These findings establish a novel role for resistin in the sex-dependent effects of PVAT in the setting of hypertension through a KATP channel-mediated mechanism
Summary
Www.nature.com/scientificreports discovered in 1991 by Soltis and Cassis who showed that PVAT asserted anti-contractile effects on vessels through so-called ‘adventitium derived relaxing factors’ (ADRF)[10]. These ADRFs affect vasorelaxation by acting through the opening of potassium channels leading to calcium influx and hyperpolarisation. The SHRSP is a well-established model of cardiovascular disease sharing many of the pathologies seen in humans; including the sex difference observed in hypertension[18] This difference is observed from 12 weeks of age, but more pronounced at 16 weeks, when the systolic blood pressure of male SHRSP is approximately 30 mmHg higher than female SHRSP19. This study used age-matched 16 week old male and female SHRSP to explore sex-dependent differences in PVAT function in hypertension using ex vivo and molecular-based studies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
