Garthoff B, Bellemann P
Institute of Pharmacology, Bayer AG, Wuppertal, F.R.G.
J Cardiovasc Pharmacol. 1987;10 Suppl 10:S36-9.
It has already been emphasized that salt-dependent hypertension might be especially sensitive to calcium antagonists, and it has recently been shown that binding at different receptor types might be altered by dietary sodium chloride. Therefore, it was of interest to find the extent to which the specific membrane-associated dihydropyridine (DHP) receptors are influenced by salt loading and/or nitrendipine treatment. Groups of 10-12 salt-sensitive (S/JR) or salt-resistant (R/JR) Dahl rats and spontaneously hypertensive rats (SHRSP) or normotensive Wistar-Kyoto rats (WKY) received diets containing low (0.4%) or high (8%) NaCl for 21 days; treated animals received 300 ppm nitrendipine additionally with the diet. Blood pressure of R/JR and WKY did not differ markedly on the different diets, whereas in hypertensive rat strains, salt loading increased blood pressure after 3 weeks. High salt resulted in an increased number of cardiac DHP receptors in SHRSP; the addition of nitrendipine enhanced DHP receptor capacity in the heart and brain membranes of both strains (SHRSP and S/JR). No major changes in affinity were observed. Augmentation in the number of DHP receptors as analyzed in a follow-up interim observation study on SHR occurred more rapidly in heart than in brain tissue. It can be concluded that an altered number of the DHP receptor sites, and not changes in affinity, might be essential during treatment with calcium antagonists. The DHP receptor sites, and not changes in affinity, might be essential during treatment with calcium antagonists. The DHP receptor density can be modified by high salt intake, as shown in salt-loaded SHRSP.
已经有人强调,盐依赖性高血压可能对钙拮抗剂特别敏感,并且最近有研究表明,饮食中的氯化钠可能会改变钙拮抗剂与不同受体类型的结合。因此,研究特定的膜结合二氢吡啶(DHP)受体受盐负荷和/或尼群地平治疗影响的程度就显得很有意义。将10 - 12只盐敏感(S/JR)或盐抵抗(R/JR)的 Dahl 大鼠以及自发性高血压大鼠(SHRSP)或正常血压的Wistar - Kyoto大鼠(WKY)分为几组,分别给予含低(0.4%)或高(8%)氯化钠的饮食,持续21天;接受治疗的动物在饮食中额外添加300 ppm的尼群地平。不同饮食条件下,R/JR和WKY的血压没有明显差异,而在高血压大鼠品系中,盐负荷在3周后会使血压升高。高盐导致SHRSP心脏中的DHP受体数量增加;添加尼群地平可增强两种品系(SHRSP和S/JR)心脏和脑膜中的DHP受体容量。未观察到亲和力有重大变化。在对SHR进行的一项后续中期观察研究中分析发现,DHP受体数量的增加在心脏中比在脑组织中发生得更快。可以得出结论,在用钙拮抗剂治疗期间,DHP受体位点数量的改变而非亲和力的变化可能至关重要。在用钙拮抗剂治疗期间,DHP受体位点而非亲和力的变化可能至关重要。如在盐负荷的SHRSP中所示,高盐摄入可改变DHP受体密度。