Published online Oct 21, 2019. doi: 10.3748/wjg.v25.i39.5953
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
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.
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.
The aim of this study was to investigate the influence of endogenous sex hormones on PHT and hyporeactivity of mesenteric arteries.
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.
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.
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.
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.