Dieguez-Lucena J L, Aranda-Lara P, Ruiz-Galdón M, García-Villanova J, Morell-Ocaña M, Reyes-Engel A
Departamento Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Málaga, Spain.
Hypertension. 1996 Jul;28(1):98-103. doi: 10.1161/01.hyp.28.1.98.
In the present study, we studied angiotensin II type 1 (AT1) and type 2 (AT2) receptor messengers by quantitative reverse transcriptase-polymerase chain reaction. We examined peripheral blood mononuclear cells from 30 healthy subjects and 50 subjects with primary hypertension, in whom angiotensin I-converting enzyme genotype was determined, before and after 15 days of treatment with different antihypertensive drugs. The medication included a calcium channel antagonist, an angiotensin I-converting enzyme inhibitor, and a beta 1-blocker. We also studied the relationship between AT1 receptor gene expression and biochemical parameters of the renin-angiotensin system. AT1 receptor messenger levels were positively correlated with plasma renin activity in both normotensive and untreated hypertensive subjects. Increases of this messenger and plasma angiotensin II levels were correlated with the D allele in the same individuals. AT1 receptor messenger levels decreased significantly with angiotensin I-converting enzyme inhibitor treatment in subjects with the DD genotype, and a significant decrease was observed in subjects with the II and ID genotypes treated with a calcium antagonist. No changes were observed in mRNA with the beta 1-blocker. We conclude that the AT2 receptor is not expressed in peripheral leukocytes and that AT1 receptor messenger levels vary in relation to angiotensin I-converting enzyme genotype and pharmacological treatment. These results suggest that angiotensin I-converting enzyme genotype may be an important factor when deciding on antihypertensive therapy in individuals with primary hypertension.
在本研究中，我们通过定量逆转录-聚合酶链反应研究了1型（AT1）和2型（AT2）血管紧张素受体信使。我们检测了30名健康受试者和50名原发性高血压患者的外周血单核细胞，在这些患者中，在使用不同抗高血压药物治疗15天前后测定了血管紧张素I转换酶基因型。药物包括钙通道拮抗剂、血管紧张素I转换酶抑制剂和β1受体阻滞剂。我们还研究了AT1受体基因表达与肾素-血管紧张素系统生化参数之间的关系。在血压正常和未经治疗的高血压受试者中，AT1受体信使水平与血浆肾素活性呈正相关。在同一受试者中，该信使和血浆血管紧张素II水平的升高与D等位基因相关。在DD基因型受试者中，血管紧张素I转换酶抑制剂治疗后AT1受体信使水平显著降低，在用钙拮抗剂治疗的II和ID基因型受试者中也观察到显著降低。使用β1受体阻滞剂时，mRNA未观察到变化。我们得出结论，AT2受体在外周白细胞中不表达，并且AT1受体信使水平因血管紧张素I转换酶基因型和药物治疗而异。这些结果表明，血管紧张素I转换酶基因型可能是决定原发性高血压患者抗高血压治疗时的一个重要因素。
