Transcriptomic response in the heart and kidney to different types of antihypertensive drug administration [heart]

To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains of (i.e., hypertensive and normotensive) rats. We chose to use six antihypertensive classes: enalapril (angiotensin converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating beta-blocker) and hydralazine. In the tested rat strains, four of six drugs, including two renin-angiotensin system (RAS) inhibitors, were effective for BP lowering, whereas the remaining two drugs were not. Besides BP lowering, there appeared to be some inter-drug heterogeneity in phenotypic changes, such as suppressed body weight (Bw) gain and Bw-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by RAS blockade, e.g., for genes in the natriuretic peptide system (Nppb and Corin) in the heart and for those in the RAS/ kallikrein-kinin system (Ren and rat Klk1 paralogs) and those related to calcium ion binding (Calb1 and Slc8a1) in the kidney. The heart data comprises of this submission and part of ArrayExpress E-MTAB-9244.为阐明与终末器官损伤改善潜在相关的抗高血压药物诱导基因表达变化，我们对两种近交系大鼠（即高血压大鼠与正常血压大鼠）给予抗高血压药物后，对其心脏与肾脏开展了体内表型评估及转录组学分析。本研究选用6类抗高血压药物：依那普利（angiotensin converting enzyme inhibitor，血管紧张素转换酶抑制剂）、坎地沙坦（angiotensin receptor blocker，血管紧张素受体拮抗剂）、氢氯噻嗪（diuretics，利尿剂）、氨氯地平（calcium-channel blocker，钙通道阻滞剂）、卡维地洛（vasodilating beta-blocker，血管扩张性β受体阻滞剂）及肼屈嗪。在受试大鼠品系中，6种药物中有4种（含2种肾素-血管紧张素系统（renin-angiotensin system, RAS）抑制剂）可有效降低血压（blood pressure, BP），其余2种则无此效果。除降压作用外，不同药物在表型变化上存在一定异质性，例如抑制体重（Body Weight, Bw）增长以及降低体重校正后的心脏重量。就转录组应答而言，大量基因呈现出显著的mRNA表达变化，且变化模式分为血压依赖性与血压非依赖性两类，同时不同靶器官间的转录组差异显著。RAS阻断剂尤其可诱导显著的mRNA表达变化，例如心脏中利钠肽系统（natriuretic peptide system）相关基因（Nppb与Corin），以及肾脏中RAS/激肽释放酶-激肽系统（kallikrein-kinin system）相关基因（Ren与大鼠Klk1旁系同源基因）和钙离子结合（calcium ion binding）相关基因（Calb1与Slc8a1）。本提交的数据集包含心脏相关数据，同时还涵盖了ArrayExpress数据库中E-MTAB-9244的部分内容。