Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R811-21. doi: 10.1152/ajpregu.00244.2011. Epub 2011 Jun 22.
Previous studies have demonstrated that chronic dietary salt loading causes hypertension and a decreased sensitivity of the systemic vasculature to α-adrenergic stimulation and other hypertensive stimuli (e.g. hypercapnia) in rainbow trout (Oncorhynchus mykiss). This reduced sensitivity to hypertensive stimuli is consistent with a possible blunting of homeostatic responses normally aimed at raising blood pressure. To test this idea, we examined the consequences of long-term salt feeding and the associated hypertension on the interactive capacities of the renin angiotensin system (RAS) and adrenergic systems to elevate blood pressure in trout. Secretion of catecholamines in response to a range of doses of homologous ANG II in vivo and in situ (using a perfused posterior cardinal vein preparation) was reduced in the salt-fed fish. The reduced sensitivity to ANG II could not be explained by alterations in stored catecholamine (adrenaline or noradrenaline) levels or the general responsiveness of the chromaffin cells to depolarizing stimuli (60 mmol/l KCl). Despite the decreased responsiveness of the chromaffin cells to ANG II, plasma catecholamines were increased to a greater extent in the salt-fed fish during acute hypoxia (a condition that activates the RAS). Interestingly, the pressor effects of ANG II in vivo were actually heightened in the salt-fed fish. The increased pressor response to exogenous ANG II was likely attributable to its direct interaction with vascular ANG II receptors because the effect persisted even after blockade of α-adrenergic receptors. Treating fish with the vascular smooth muscle relaxant papaverine caused similar reductions in blood pressure and increases in plasma ANG II levels regardless of diet. Similarly, inhibition of angiotensin converting enzyme with lisinopril reduced blood pressure equally in control and salt-fed fish. These results indicate that, while long-term dietary salt loading blunts the response of trout chromaffin cells to ANG II, the RAS itself appears to be unaffected. Indeed, the capacity of ANG II to elevate blood pressure is not compromised nor do fish exhibit a reduced capacity to mount an acute humoral adrenergic stress response during acute hypoxia.
先前的研究表明，慢性膳食盐负荷会导致高血压以及虹鳟鱼（Oncorhynchus mykiss）全身血管对 α-肾上腺素能刺激和其他高血压刺激（如高碳酸血症）的敏感性降低。这种对高血压刺激的敏感性降低与可能削弱旨在升高血压的体内平衡反应一致。为了验证这一观点，我们研究了长期盐喂养和相关高血压对虹鳟鱼血压升高的肾素血管紧张素系统（RAS）和肾上腺素能系统相互作用能力的影响。在盐喂养的鱼中，体内和原位（使用灌注后的后冠状静脉制备）对同源 ANG II 的一系列剂量的儿茶酚胺分泌减少。对 ANG II 敏感性降低不能用储存儿茶酚胺（肾上腺素或去甲肾上腺素）水平的改变或嗜铬细胞对去极化刺激（60mmol/l KCl）的一般反应性来解释。尽管嗜铬细胞对 ANG II 的反应性降低，但在急性缺氧期间（激活 RAS 的条件），盐喂养的鱼中的血浆儿茶酚胺增加到更大程度。有趣的是，盐喂养的鱼体内 ANG II 的加压作用实际上增强了。对外源 ANG II 的加压反应增加可能归因于其与血管 ANG II 受体的直接相互作用，因为即使在阻断 α-肾上腺素能受体后，该作用仍然持续。用血管平滑肌松弛剂罂粟碱处理鱼会导致无论饮食如何，血压降低和血浆 ANG II 水平升高相似。同样，用赖诺普利抑制血管紧张素转换酶在对照和盐喂养的鱼中同样降低血压。这些结果表明，虽然长期膳食盐负荷会使虹鳟鱼嗜铬细胞对 ANG II 的反应迟钝，但 RAS 本身似乎不受影响。事实上，ANG II 升高血压的能力没有受到损害，鱼在急性缺氧期间也没有表现出降低的急性体液肾上腺素应激反应能力。
