The kidney failure in hepatorenal syndrome is believed to arise from abnormalities in blood vessel tone in the kidneys. The predominant theory (termed the "underfill" theory) is that blood vessels in the kidney circulation are constricted because of the dilation of blood vessels in the splanchnic circulation (which supplies the intestines), which is mediated by factors released by liver disease. Nitric oxide, prostaglandins, and other vasoactive substances have been hypothesized as powerful mediators of splanchnic vasodilation in cirrhosis. The consequence of this phenomenon is a decrease in the "effective" volume of blood sensed by the juxtaglomerular apparatus, leading to the secretion of renin and the activation of the renin–angiotensin system, which results in the vasoconstriction of vessels systemically and in the kidney specifically. However, the effect of this is insufficient to counteract the mediators of vasodilation in the splanchnic circulation, leading to persistent "underfilling" of the kidney circulation and worsening kidney vasoconstriction, leading to kidney failure.