靜脈投與脂肪乳劑和中樞投與非酯化脂肪酸對於感壓接受器反射敏感度的影響

1. 靜脈投與脂肪乳劑和中樞投與非酯化脂肪酸對於感壓接受器反射敏感度的影響靜脈投與脂肪乳劑和中樞投與非酯化脂肪酸對於感壓接受器反射敏感度的影響 • 許多研究指出肥胖和高血壓關係密切，肥胖常伴隨高血脂症(hyperlipoproteinemia)之發生，而高血脂症和高血壓之間也有密不可分的關係，由於肥胖、高血脂與高血壓三者間的密切關連，高血脂是否影響血壓調節是本篇研究所要探討的主題。感壓接受器反射(baroreceptor reflex，BRR)是血壓調節的重要機制，而高血壓患者之感壓接受器反射敏感度(baroreceptor reflex sensitivity，BRRS)通常較低，我們探討的第一個問題是高血脂是否影響感壓接受器反射敏感度。另外，肥胖者之高血脂狀況使血中的非酯化脂肪酸(nonesterified fatty acids，NEFAs)濃度比非肥胖者高，NEFAs可以輕易地通過血腦屏障進入中樞神經系統，已有不少研究顯示NEFAs作用於中樞神經細胞，調節神經細胞的活性，因此我們推測肥胖所造成之血液中較高濃度之NEFAs可能到達中樞神經系統。我們提出一個推論，肥胖所造成之血液中較高濃度之NEFAs可能作用於中樞神經系統，影響血壓的調控，是肥胖型高血壓的形成原因之一，也可能是高血脂影響血壓調控的機轉之一。因此本研究探討的第二個問題是中樞投與NEFAs對血壓之調控的影響。針對第一個問題，高血脂是否影響BRRS，我們對Sprague－Dawley(SD)雄性成鼠進行靜脈輸注(intravenous infusion，縮寫為IV infusion)投與IntralipidTM 20％模擬高血脂狀態，觀察其對於BRRS的影響，結果發現IV infusion投與IntralipidTM 20％有意義的降低phenylephrine所引起之BRRS，此發現支持前述高血脂會影響BRRS的假說；我們同時測得IV infusion投與IntralipidTM 20％之後，血漿中的NEFAs濃度上升，因此我們推測IntralipidTM 20％中的NEFAs會降低phenylephrine所引起之BRRS。針對第二個問題，中樞投與NEFAs是否影響血壓的調控，我們對SD雄性成鼠施與側腦室注射(intracerebroventricular injection，縮寫為ICV injection)投與NEFAs，觀察NEFAs對於BRRS的影響，結果發現在ICV injection投與硬脂酸(stearate)之後phenylephrine所引起之BRRS明顯下降，而投與亞麻油酸(linoleic acid)後，phenylephrine所引起之BRRS則是明顯升高，至於ICV injection投與棕櫚酸(palmitate)、油酸(oleic acid)或花生四烯酸(arachidonic acid)後，phenylephrine所引起之BRRS並沒有顯著的差異。此外，IV injection投與各種NEFAs後對於phenylephrine所引起之BRRS都並無顯著的差異，因此推測ICV injection投與之NEFAs可能作用於中樞神經系統而影響BRRS。根據本研究結果，肥胖者之高血脂狀況使血中NEFAs濃度上升，而NEFAs可能作用於中樞神經系統而影響BRRS以改變血壓調節的功能，並可能是導致高血壓的原因之ㄧ。

2. Effects of Intravenously Applied Fat Emulsion and Centrally Applied Nonesterified Fatty Acids (NEFAs) on Baroreceptor Reflex Sensitivity • A positive correlation between obesity and hypertension has been confirmed in many epidemiological studies while the underlying mechanisms have yet to be defined. Obesity is often accompanied by hyperlipoproteinemia, which is also a risk factor of hypertension. A question whether hyperlipoproteinemia leads to changes in the regulatory machineries of the cardiovascular function and in turn underlies the mechanisms linking obesity and hypertension is, therefore, brought up. In the present study, the effects of hyperlipoproteinemia and nonesterified fatty acids (NEFAs), the hydrolytic products of lipoproteins, on the baroreceptor reflex sensitivity (BRRS) were examined.BRRS was reduced by intravenous (iv) infusion of IntralipidTM 20％, while arterial pressure and heart rate were not changed. These observations imply that elevated plasma lipids impairs BRRS. Plasma NEFAs raised following an iv infusion of IntralipidTM 20％. To examine whether NEFAs are capable of regulating BRRS and thus contribute to the impairment of BRRS by IntralipidTM 20％, NEFAs were administered centrally (intracerebroventricularly, icv) and systemically (iv). We found that, by icv adiministration, stearate decreased BRRS, whereas linoleic acid increased BRRS. No significant changes of BRRS was observed with icv administration of oleic acid, palmitate and arachidonic acid as well as iv administration of all four kinds of NEFAs did not affect BRRS. These finding suggest that NEFAs acting centrally to affect BRRS may be responsible for the impairment of BRRS caused by iv IntralipidTM 20％. The results implicate that lipid abnormalities may contribute to the elevated blood pressure in hypertensive subjects via impairment of the BRRS.