| Summary: | The regulation of local metabolism is intimately related to blood flow. Vasoactive substances, such as nitric oxide (NO), prostaglandins and adenosine, are involved in the regulation of hepatic and intestinal blood flow and metabolism. These substances and other vascular factors interact. The general hypothesis of the thesis is that the functional homeostasis of an organ is achieved through the interaction of different factors at the levels of both hemodynamics and metabolism, and the regulation of local hemodynamics meets the requirement of metabolism and maintains physiological integrity. Several aspects in hemodynamics-related regulation of glucose and oxygen metabolism in the liver and intestine were addressed in this thesis using 'in vivo' animal models. My results showed that the inhibition of NO potentiated the vasoconstrictor effect of norepinephrine, and norepinephrine slightly suppressed the vasodilator effects of adenosine and isoproterenol in the hepatic artery. However, blockade of NO substantially potentiated the suppression by norepinephrine of the vasodilation, suggesting that NO strongly inhibited the effects of norepinephrine in the interaction, although NO is not involved in control of basal hepatic arterial tone. Having shown that NO inhibited the vascular effect of norepinephrine, the influence of NO on norepinephrine-induced hepatic glycogenolysis was further investigated. NO potentiated norepinephrine-induced glycogenolysis while it inhibited the vasoconstrictor effect. NO antagonizes adenosine vasodilator effects in the intestine. The results in the thesis further demonstrated that NO, either released endogenously by shear stress or introduced exogenously, inhibited the metabolic effect of adenosine in the intestine, suggesting that NO antagonized adenosine also at the metabolic level. The mechanism of the regulation of intestinal glucose utilization is not clear. It was hypothesized t at the release of autacoids by elevated shear stress, secondary to increased blood flow, mediates increased intestinal glucose uptake from the blood. My experiments discovered that prostaglandin F 2_ mediated the increase in intestinal glucose uptake when blood flow was increased. The results in this thesis provided more evidence that the vasoactive substances interact at hemodynamic and metabolic levels, supporting the concept that the system maintains a hemodynamic and metabolic homeostasis hrough the interaction of these substances and factors.
|
|---|
