ENDOTHELIUM-DEPENDENT RELAXATION AND L-ARGININE METABOLISM IN GENETIC-HYPERTENSION
ENDOTHELIUM-DEPENDENT RELAXATION AND L-ARGININE METABOLISM IN GENETIC-HYPERTENSION
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DOI：
10.1161/01.hyp.19.5.435
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发表时间：
1992-05-01
期刊：
影响因子：
8.3
通讯作者：
WEBB, RC
中科院分区：
文献类型：
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作者：
LEE, L;WEBB, RC
本研究研究了l -精氨酸和N(G)-单甲基l -精氨酸对Wistar-Kyoto大鼠和卒中易发自发性高血压大鼠血管组织扩张剂反应性的影响。将腹主动脉环悬挂于组织浴中测量等距力。在苯肾上腺素引起收缩后，在肌液中累积添加乙酰胆碱、l -精氨酸或A23187，在两组动物中引起相似的主动脉环松弛。为了验证精氨酸代谢在高血压中改变的假设，我们用N(G)-单甲基l -精氨酸孵育主动脉环。N(G)-单甲基l -精氨酸（10-300 μ M）不影响两组动物对苯肾上腺素（10（-10）至10(-4)M）的收缩反应（EC50, 10(-7) M）。高血压动物的主动脉环暴露于N(G)-单甲基l -精氨酸导致对乙酰胆碱（10（-10）至10(-6)M）松弛反应的更大抑制。N(G)-单甲基l -精氨酸（300 mu- m）引起高血压组对乙酰胆碱松弛的完全抑制。l -精氨酸（10-100 μ m）孵育克服了N(G)-单甲基l -精氨酸对乙酰胆碱诱导的松弛的抑制作用。两组主动脉环段暴露于N(G)-单甲基l -精氨酸可减弱对A23187的松弛反应（10（-10）至3 X 10(-6) M）。l -精氨酸诱导的N(G)单甲基l -精氨酸对A23187松弛反应的抑制作用逆转在两组间相似。我们得出的结论是，与Wistar-Kyoto大鼠相比，N(G)单甲基l -精氨酸对乙酰胆碱反应的内皮源性松弛因子产生的抑制作用在卒中易发的自发性高血压大鼠中更大。这一发现反映了遗传性高血压中l -精氨酸代谢的差异，这可能是导致血管反应性改变的重要因素。
This study characterizes the effects of L-arginine and N(G)-monomethyl L-arginine on dilator responsiveness of vascular tissue from Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. Rings of abdominal aorta were suspended in tissue baths for measurement of isometric force. After contraction induced by phenylephrine, cumulative addition of acetylcholine, L-arginine, or A23187 to the muscle bath caused a similar relaxation of aortic rings in both animal groups. To test the hypothesis that arginine metabolism is altered in hypertension, aortic rings were incubated with N(G)-monomethyl L-arginine. N(G)-monomethyl L-arginine (10-300-mu-M) did not affect contractile responses to phenylephrine (10(-10) to 10(-4) M) in either animal group (EC50, 10(-7) M). Exposure of aortic rings to N(G)-monomethyl L-arginine resulted in a greater inhibition of relaxation response to acetylcholine (10(-10) to 10(-6) M) in hypertensive animals. N(G)-monomethyl L-arginine (300-mu-M) caused complete inhibition of relaxation to acetylcholine in the hypertension group. Incubation with L-arginine (10-100-mu-M) overcame the inhibition of acetylcholine-induced relaxation produced by N(G)-monomethyl L-arginine in both groups. Exposure of aortic ring segments to N(G)-monomethyl L-arginine attenuated relaxation responses to A23187 (10(-10) to 3 X 10(-6) M) in both groups. L-Arginine-induced reversal of the inhibitory effect of N(G) monomethyl L-arginine on the relaxation responses to A23187 was similar between groups. We conclude that the inhibitory effect of N(G) monomethyl L-arginine on endothelium-derived relaxing factor production in response to acetylcholine is greater in stroke-prone spontaneously hypertensive rats as compared with Wistar-Kyoto rats. This finding reflects differences in L-arginine metabolism in genetic hypertension that may be an important factor in contributing to altered vascular reactivity.