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Project description: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. This submission includes the kidney data.
2022-04-15 | GSE188349 | GEO
Project description: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.
2022-04-15 | GSE188348 | GEO
Project description: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 -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 E-MTAB-9244.
2022-04-15 | E-MTAB-10667 | biostudies-arrayexpress
Project description: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. This submission includes the kidney data.
2022-04-15 | E-MTAB-10672 | biostudies-arrayexpress
Project description:Transcriptomic response in the heart and kidney to different types of antihypertensive drug administration [heart]
| PRJNA778413 | ENA
Project description:Transcriptomic response in the heart and kidney to different types of antihypertensive drug administration [kidney]
| PRJNA778414 | ENA
Project description:Transcriptomic response in the heart and kidney to different types of antihypertensive drug administration
| PRJNA778412 | ENA
Project description:To determine whether office, home, ambulatory daytime and nighttime blood pressure (BP) responses to antihypertensive drug therapy measure the same signal and which method provides greatest power to identify genetic predictors of BP response.We analyzed office, home, ambulatory daytime and nighttime BP responses in hypertensive adults randomized to atenolol (N = 242) or hydrochlorothiazide (N = 257) in the Pharmacogenomic Evaluation of Antihypertensive Responses Study. Since different measured BP responses may have different predictors, we tested the "same signal" model by using linear regression methods to determine whether known predictors of BP response depend on the method of BP measurement. We estimated signal-to-noise ratios and compared power to identify a genetic polymorphism predicting BP response measured by each method separately and by weighted averages of multiple methods.After adjustment for pretreatment BP level, known predictors of BP response including plasma renin activity, race, and sex were independent of the method of BP measurement. Signal-to-noise ratios were more than 2-fold greater for home and ambulatory daytime BP responses than for office and ambulatory nighttime BP responses and up to 11-fold greater for weighted averages of all four methods. Power to identify a genetic polymorphism predicting BP response was directly related to the signal-to-noise ratio and, therefore, greatest with the weighted averages.Since different methods of measuring BP response to antihypertensive drug therapy measure the same signal, weighted averages of the BP responses measured by multiple methods minimize measurement error and optimize power to identify genetic predictors of BP response.
| S-EPMC3342146 | biostudies-literature
Project description:Quality and quantity of home blood pressure (BP) control are important for optimizing hypertensive treatment. The prevalence and associated clinical characteristics of the different home blood pressure phenotypes in treated hypertensive patients were not elucidated. This study was conducted in Siriraj Hospital, Thailand from 2019 to 2020. We included treated hypertensive patients with ≥1 antihypertensive drug and had self-home BP measurement data. Both traditional (office BP < 140/90 mmHg and home BP < 130/80 mmHg) and new BP targets (office and home BP < 130/80 mmHg) were used for the classification of BP phenotypes. Home BP phenotypes consisted of controlled hypertension (all home BPs achieved home BP targets), isolated uncontrolled morning hypertension (MoHT) (only morning BP was above home BP targets), isolated uncontrolled evening hypertension (EHT) (only evening BP was above home BP targets), and combined morning-evening uncontrolled hypertension (MoEHT) (all home BPs were above home BP targets). Our study included 1,406 patients. The total mean age was 62.94 ± 13.97 years. There were 39.40% men. The prevalence of each home BP phenotype (by traditional BP target) was 55.76%, 12.66%, 7.40%, and 24.18% in controlled (home) hypertension, MoHT, EHT, and MoEHT, respectively. Classical BP control status was 35.21% well-controlled hypertension, 30.01% white-coat uncontrolled hypertension, 9.74% masked uncontrolled hypertension, and 25.04% sustained uncontrolled hypertension. The multivariable analysis showed the significantly associated factor of MoHT was the presence of previous cardiovascular disease (adjusted OR 5.54, 95% CI (2.02-15.22); p value = 0.001). Taking once-daily long-acting antihypertensive drugs in the morning were significantly associated with both EHT (adjusted OR 0.20, 95% CI (0.05-0.82); p value = 0.025) and MoEHT (adjusted OR 0.20, 95% CI (0.04-1.00); p value = 0.049). These results were consistent in groups classified by new home BP target <130/80 mmHg.
| S-EPMC9754835 | biostudies-literature
Project description:PurposeThe objective of this study was to compare different techniques to enhance the solubility and dissolution rate, and hence the bioavailability of candesartan cilexetil.MethodsTo achieve this target, various techniques were employed such as solid dispersions, inclusion complexes, and preparation of candesartan nanoparticles. Following the preparations, all samples were characterized for their physicochemical properties, and the samples of the best results were subjected to further bioavailability studies.ResultsResults of dissolution studies revealed an increase in the dissolution rate of all samples. The highest dissolution rate was achieved using solid dispersion of the drug with PVP K-90 (1:4). Physicochemical investigations (XR, DSC, and FT-IR) suggested formation of hydrogen bonding and changing in the crystalline structure of the drug. Regarding the inclusion complexes, more stable complex was formed between HP-β-CD and CC compared to β-CD, as indicated by phase solubility diagrams. Antisolvent method resulted in the preparation of stable nanoparticles, as indicated by ζ potential, with average particle size of 238.9 ± 19.25 nm using PVP K-90 as a hydrophilic polymer. The best sample that gave the highest dissolution rate (CC/PVP K-90 1:4) was allowed for further pharmacokinetic studies using UPLC MS/MS assay of rabbit plasma. Results showed a significant increase in the bioavailability of CC from ~15% to ~48%.ConclusionThe bioavailability of CC was significantly improved from ~15% to ~48% when formulated as SDs with PVP K-90 with 1:4 drug:polymer ratio.
| S-EPMC7234962 | biostudies-literature