Membrane abnormalities in hypertension

本项目的目的是阐明高血压患者的细胞膜异常。首先，我们检测了高血压患者血管内突触膜功能和交感神经传递的变化。分离自发性高血压大鼠(SHR)和DOCA-盐性高血压大鼠的肠系膜血管。幼年SHR和慢性DOCA-盐性高血压患者对电刺激神经或外源性去甲肾上腺素(NE)的血管收缩反应和肾上腺素能神经末梢的内源性NE溢出反应均显著高于年龄匹配的正常血压对照组。突触前肾上腺素受体、前列腺素E_2、多巴胺、肽类激素对去甲肾上腺素溢出的抑制作用在自发性高血压大鼠明显减弱。而钙拮抗剂、钙调蛋白拮抗剂或&lt；Na+&gt；，&lt；K^+&gt；-ATPase抑制剂在这些高T拮抗剂或&lt；Na+&gt；，&lt；K^+&gt；-…中对去甲肾上腺素溢出的作用增强在这些高血压模型中，对去甲肾上腺素外溢的抑制作用比对照组更强。第二，我们利用从高血压患者和自发性高血压患者获得的红细胞膜的物理化学性质进行了研究。高血压病患者红细胞钠含量和Na-Li逆向转运均高于正常血压对照组。钙对红细胞渗透脆性(用螺旋离心机测定)和红细胞膜流动性(用电子自旋共振法测定)影响很大。此外，钙引起的渗透脆性和膜流动性的降低在高血压和自发性高血压患者中比正常血压对照组更为明显。这些结果表明，突触膜功能的改变，对血管降压素的反应减弱，膜的物理化学性质或钙敏感性的异常可引起交感神经活动和血管反应性的过度增强，这可能至少部分地参与了高血压的发病。较少

The purpose of this project was to elucidate the membrane abnormalities in hypertension. Firstly, we have examined alterations of synaptic membrane functions and sympathetic neurotransmission in blood vessels of hypertension. Isolated mesenteric vasculatures were prepared from spontaneously hypertensive rats (SHR) and DOCA-salt hypertension in rats. The vasoconstrictor responses to electrical nerve stimulation or exogenous norepinephrine (NE) as well as endogenous NE overflow from the adrenergic nerve endings were significantly increased in young SHR and chronic DOCA-salt hypertension compared with their age-matched normotensive controls. The inhibitory modulations of NE overflow by presynaptic <alpha_2> -adrenoceptors, prostaglandin <E_2> ,dopamine, peptide hormones were attenuated in SHR than in controls. Whereas, the effects of Ca-antagonists, calmodulin-antagonists or <Na^+> , <K^+> -ATPase inhibitors on NE overflow were enhanced in these hypert antagonists or <Na^+> , <K^+> -ATPas … More e inhibitors on NE overflow were enhanced in these hypertensive models than in their controls.Secondly, we have investigated physicochemical properties of cell membranes by use of erythrocytes obtained from patients with essential hypertension and SHR. The sodium content and Na-Li countertransport were increased in erythrocytes from essential hypertension compared with those in normotensive controls. Osmotic fragility of erythrocytes (determined by Coil Planet Centrifuge System) and erythrocyte membrane fluidity (determined by electron spin resonance method) were much affected by calcium. Further, these Ca-induced reductions of osmotic fragility and membrane fluidity were more prominent in essential hypertension and SHR compared with those in their normotensive controls.These results suggest that alterations of synaptic membrane functions, attenuated responsiveness to vasodepressor hormones and abnormalities of physicochemical properties or Ca-sensitivity of the membranes could induce an exaggerated sympathetic nerve activity and vascular reactivity, which might contribute, at least partially, to the pathogenesis of hypertension. Less