Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2019; 25(39): 5953-5960
Published online Oct 21, 2019. doi: 10.3748/wjg.v25.i39.5953
Gender differences in vascular reactivity of mesenteric arterioles in portal hypertensive and non-portal hypertensive rats
Bin Zhang, Lin-Hua Ji, Cheng-Gang Zhang, Gang Zhao, Zhi-Yong Wu
Bin Zhang, Lin-Hua Ji, Cheng-Gang Zhang, Gang Zhao, Zhi-Yong Wu, Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Author contributions: Zhang B, Zhao G, and Wu ZY designed the research; Ji LH, Zhang B, and Zhang CG performed the research; Zhang B and Zhang CG analyzed the data; Ji LH and Zhang B wrote the paper.
Supported by the National Natural Science Foundation for the Youth of China, No. 81400630
Institutional review board statement: The study was reviewed and approved by Renji Hospital Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Renji Hospital (IACUC protocol number: RJ-20151211).
Conflict-of-interest statement: The authors declare that there is no conflict of interest to be disclosed.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE Guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Gang Zhao, MD, PhD, Chief Doctor, Surgeon, Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Shanghai 200127, China. zhaogang@renji.com
Telephone: +86-21-68383732 Fax: +86-21-68383090
Received: July 25, 2019
Peer-review started: July 25, 2019
First decision: August 17, 2019
Revised: August 28, 2019
Accepted: September 9, 2019
Article in press: September 9, 2019
Published online: October 21, 2019
Processing time: 87 Days and 21.2 Hours
ARTICLE HIGHLIGHTS
Research background

Portal hypertension (PHT) is primarily caused by an increase in resistance to portal outflow and secondarily by an increase in splanchnic blood flow. Vascular hyporeactivity both in systemic circulation and in the mesenteric artery plays a role in the hyperdynamic circulatory syndrome. Gender differences in the incidence of liver cirrhosis, PHT and vascular responsiveness have been demonstrated by some epidemiological and experimental studies. Cirrhotic rats treated with estradiol showed a significant decrease in portal pressure and a significant increase in hepatic blood flow, consistent with increased nitric oxide synthase in sinusoidal endothelial cells and inhibited activation of hepatic stellate cells. Previous studies on vascular reactivity mostly used isolated aorta, peripheral arteries, or mesenteric arteries. In this study of vascular reactivity, we investigated the change in inner diameter of the third branches of the mesenteric arteries (diameter ~100 μm) under the microamplification system.

Research motivation

Despite the increased level of circulating endogenous vasoconstrictors in PHT, the sensitivity of blood vessels to them is significantly reduced. The pathogenetic mechanisms of this phenomenon have not been fully investigated.

Research objectives

The aim of this study was to investigate the influence of endogenous sex hormones on PHT and hyporeactivity of mesenteric arteries.

Research methods

Cirrhosis and PHT were established by subcutaneous injection of CCl4 in both male and female integral and castrated rats (ovariectomized [OVX] in female rats, orchiectomy [ORX] in male rats). The third-order branch of the mensenteric artery was divided and used to measure vascular reactivity to vasoconstrictors. The third-order arterioles of the mesentery were carefully dissected and transferred to a vascular perfusion system. Two glass micropipettes (top diameter, 50 μm) were inserted into each end of the arteriole. Cumulative norepinephrine (NE) concentration response curves (10-8 mol/L-10-4 mol/L) were obtained by increasing the concentration in quarter-log increments.

Research results

ORX decreased the sensitivity to vasoconstrictors of the mesenteric arterioles of non-PHT male rats, indicating that androgen affects vascular tone in physiological conditions. However, in cirrhotic and PHT rats, conservation of androgens had little effect on the vascular reaction to vasoconstrictors. OVX had no effect on the vascular reaction to NE in non-PHT female rats. Compared to OVX female PHT rats, the sensitivity of mesenteric arterioles to NE in integral female PHT rats was enhanced, indicating that conservation of estrogen can retain the sensitivity of the mesenteric arterioles to vasoconstrictors and has a protective effect on splanchnic vascular function in PHT.

Research conclusions

Clear gender differences were observed in mesenteric vascular reactivity in carbon tetrachloride-induced cirrhotic and PHT rats. Conservation of estrogen can retain the sensitivity of the mesenteric arterioles to vasoconstrictors and has a protective effect on splanchnic vascular function in PHT.

Research perspectives

Estrogen can improve hyporeactivity of the splanchnic arteries to vasoconstrictors, while androgens cannot. Endothelial NO synthase and NO production, oxidative stress, and some signal pathways may participate in the underlying mechanism.