Lais L T, Brody M J
Eur J Pharmacol. 1978 Jan 15;47(2):177-89. doi: 10.1016/0014-2999(78)90389-8.
Factors which play a primary role in the initiation and development of hypertension in spontaneously hypertensive rats (SHR) are incompletely defined. To test the possibility that early changes in vascular function play a primary etiologic role, hindquarters of 3-week-old SHR and Wistar-Kyoto normotensive rats (WKY) were perfused at constant flow with plasma substitute. The vasculature of SHR exhibited higher resistance to flow than that of WKY. The threshold constrictor response to norepinephrine (NE) was elicited at a significantly lower concentration (6X) than required in WKY, while threshold to BaCl2 was not different. At concentrations of BaCl2 above threshold, SHR exhibited marked hyperresponsiveness compared to WKY. This resulted in a greater maximum response and thus a steeper slope. The ED50 for BaCl2 was not different. A similar dose--response relationship (greater maximum, steeper slope) was observed with NE except that the ED50 as well as threshold was significantly lower in SHR than in WKY. These data show that vasoconstrictor hyperresponsiveness and increased vascular resistance are present at the time when the hypertension is first detectable. The hyperresponsiveness includes two distinct components: (1) A specific hypersensitivity to NE and (2) non-specific hyperresponsiveness which could derive from altered excitation--contraction coupling and/or from a structural mechanism already present when pressure differences begin to appear.
在自发性高血压大鼠（SHR）中，引发和发展高血压的主要因素尚未完全明确。为了测试血管功能的早期变化是否起主要病因作用，对3周龄SHR和Wistar-Kyoto正常血压大鼠（WKY）的后肢以恒定流量灌注血浆代用品。SHR的血管系统对血流的阻力高于WKY。去甲肾上腺素（NE）引起的阈值收缩反应所需浓度（6倍）明显低于WKY，而对BaCl2的阈值无差异。在高于阈值的BaCl2浓度下，与WKY相比，SHR表现出明显的高反应性。这导致了更大的最大反应，从而斜率更陡。BaCl2的半数有效剂量（ED50）无差异。除了SHR的ED50和阈值明显低于WKY外，NE也观察到类似的剂量-反应关系（更大的最大值，更陡的斜率）。这些数据表明，在首次检测到高血压时就存在血管收缩高反应性和血管阻力增加。高反应性包括两个不同的成分：（1）对NE的特异性超敏反应和（2）非特异性高反应性，其可能源于兴奋-收缩偶联的改变和/或源于压力差开始出现时就已存在的结构机制。
