Membrane abnormalities in hypertension

本项目的目的是阐明高血压的膜异常。首先，我们研究了高血压血管突触膜功能和交感神经传递的改变。制备了自发性高血压大鼠（SHR）和doca盐性高血压大鼠的肠系膜离体血管。年轻SHR和慢性doca盐高血压患者对电神经刺激或外源性去甲肾上腺素（NE）以及肾上腺素能神经末梢内源性NE溢出的血管收缩反应，与同龄正常血压对照组相比显著增加。SHR组突触前<alpha_2> -肾上腺素、前列腺素< e__2 >、多巴胺、肽激素对NE溢出的抑制作用较对照组减弱。然而，钙拮抗剂、钙调素拮抗剂或<Na^+>、<K^+> - atp酶抑制剂对NE溢出的作用在这些高压拮抗剂或<Na^+>、<K^+> - atp酶抑制剂中得到增强。其次，我们利用从原发性高血压和SHR患者身上获得的红细胞，研究了细胞膜的理化性质。原发性高血压患者红细胞中钠含量和钠-李反转运均高于正常对照组。红细胞的渗透脆性（用螺旋行星离心系统测定）和细胞膜流动性（用电子自旋共振法测定）受钙的影响较大。此外，与正常血压对照组相比，钙诱导的渗透脆弱性和膜流动性的降低在原发性高血压和SHR中更为明显。这些结果表明，突触膜功能的改变、对血管抑制激素的反应性减弱以及膜的物理化学性质或钙敏感性的异常可能导致交感神经活动和血管反应性的过度，这可能至少部分地参与了高血压的发病机制。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