Models of Experimental Hypertension in Mice

Johns, Conrado; Gavras, Irène; Handy, Diane E.; Salomao, A.; Gavras, Haralambos

doi:10.1161/01.hyp.28.6.1064

Cited by 156 publications

(155 citation statements)

References 33 publications

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“…Q-RT-PCR, run in triplicate and including negative controls, were performed using total RNA from the brain, kidney, aorta, and heart of mice infused with ANG II (n ϭ 6) or saline (n ϭ 6) for 6 h (6 hr); ANG II (n ϭ 6) or saline (n ϭ 6) for 7 days (7D), and ANG II (n ϭ 7) or saline (n ϭ 8) for 14 days (14D). The heart salt sample shown in B was obtained from mice subjected to subtotal nephrectomy, as previously described (23,29). After subtotal nephrectomy, experimental animals in this group were placed and maintained on 1% NaCl as drinking water for a maximal period of 35 days.…”

Section: Discussionmentioning

confidence: 99%

“…The animals were housed in the animal quarters, and all experiments were conducted in accordance with the "Guidelines for the Care and Use of Animals" approved by the Boston University School of Medicine. Continuous infusion of 0.9 g/h ANG II (n ϭ 6) or saline (n ϭ 6) was carried out via subcutaneous osmotic minipumps (Alzet model 2001; Alza; Palo Alto, CA) for 7 days, as previously described (23,41). Systolic blood pressure (BP) and heart rate measurements were obtained daily in conscious mice using a computerized, noninvasive tail-cuff system (model BP 2000, Visitech Systems).…”

Section: Methodsmentioning

confidence: 99%

“…In the 6-h treatment group, the mean arterial pressure was recorded with a computerized data-acquisition system (Power Laboratory/400, ADInstruments) after direct catheterization of the iliac artery and connection of the arterial line to a BP transducer, as described elsewhere (23). At 6 h of ANG II (n ϭ 7) or saline (n ϭ 6) treatment, the mean arterial pressure values were, respectively, 134 Ϯ 7.38 and 102.2 Ϯ 9.15 mmHg.…”

Section: Methodsmentioning

confidence: 99%

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Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression

Schwartz¹,

Duka²,

Duka³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Schwartz, Faina, Arvi Duka, Irena Duka, Jing Cui, and Haralambos Gavras. Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression. Am J Physiol Heart Circ Physiol 287: H1957-H1966, 2004. First published July 8, 2004 doi:10.1152/ajpheart.00568.2004.-Although the central role of ANG II in cardiovascular homeostasis is well appreciated, the molecular circuitry of its many actions is not completely understood. With the use of serial analysis of gene expression to assess global transcriptional changes in the heart of mice after continuous 7-day ANG II administration, we identified patterns of gene expression indicative of cardiac remodeling, including coordinate regulation of genes previously described in a context of processes associated with hypertrophy and fibrosis. In addition, we discovered several novel ANG II targets, including characterized genes of known function, recently annotated genes of unknown function, and the putative genes not yet present in current databases. The serial analysis of gene expression approach to assess the role of ANG II presented in this report provides new venues for inquiries into ANG II-mediated cardiac function.genome-wide transcriptional profiling; hypertension; cardiac remodeling; hypertrophy; fibrosis THE KEY ROLE of ANG II in cardiovascular homeostasis is well documented. Although initially known for its vasoconstrictive action, the adverse effects of ANG II elevation on the heart independent of its hemodynamic influence were recognized in the early 1970s (7, 16), and the cardioprotective outcomes of the pharmacological interventions that either prevent the ANG II formation from the inactive angiotensinogen precursor (14) or inhibit its interaction with specific receptors (15, 48) are now well appreciated in clinical practice (6,13,17).Experimental animal studies have shown that ANG II administration can cause multifocal myocardial lesions (16, 47), and, via ANG II type 1 receptors, directly induce cardiac remodeling that involves myocyte hypertrophy (9, 25), fibroblast proliferation, and subsequent fibrosis (47), thus leading to the development of pathological cardiac hypertrophy and, ultimately, heart failure. Both in vivo and in vitro studies revealed that the ANG II effects in the heart are accompanied by changes in gene expression in the cardiac myocytes, fibroblasts, and endothelial cells (24). While the queries of selected ANG II targets supplied important information on several molecular pathways underlying the physiological and pathophysiological actions of ANG II, an all-inclusive view is provided by the genome-wide transcriptional profiling that offers an opportunity to connect separate pieces of the puzzle through the identification of the new players not intuitively obvious from our present understanding of physiology. Thus simultaneous evaluation of 4,000 genes by the use of microarray technology to query the quantitative changes in left ventricular RNA in response to ANG II-induced progression, and, subsequently, regre...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression

Schwartz¹,

Duka²,

Duka³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

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“…Thereafter, studies were conducted using three Kent Coda-6 systems (Kent Scientific) to increase throughput, allowing a larger number of mice to be measured within a 4-h period. Mice were acclimated to the BP systems over several days (50). Baseline BP then was established for each animal as the average of three sets of readings acquired on separate days with no significant difference in the sets of measurements for each mouse.…”

Section: Methodsmentioning

confidence: 99%

Endostatin lowers blood pressure via nitric oxide and prevents hypertension associated with VEGF inhibition

Sunshine¹,

Dallabrida²,

Durand³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Antiangiogenesis therapy has become a vital part of the armamentarium against cancer. Hypertension is a dose-limiting toxicity for VEGF inhibitors. Thus, there is a pressing need to address the associated adverse events so these agents can be better used. The hypertension may be mediated by reduced NO bioavailability resulting from VEGF inhibition. We proposed that the hypertension may be prevented by coadministration with endostatin (ES), an endogenous angiogenesis inhibitor with antitumor effects shown to increase endothelial NO production in vitro. We determined that Fc-conjugated ES promoted NO production in endothelial and smooth muscle cells. ES also lowered blood pressure in normotensive mice and prevented hypertension induced by anti-VEGF antibodies. This effect was associated with higher circulating nitrate levels and was absent in eNOS-knockout mice, implicating a NO-mediated mechanism. Retrospective study of patients treated with ES in a clinical trial revealed a small but significant reduction in blood pressure, suggesting that the findings may translate to the clinic. Coadministration of ES with VEGF inhibitors may offer a unique strategy to prevent drug-related hypertension and enhance antiangiogenic tumor suppression.

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“…A 7-day training period is recommended to accustom the animals to the restrainers. [2][3][4] Nevertheless, heart rates recorded while mice are in a restrainer are higher than those in the resting state. 3 Furthermore, blood pressures also appear to be higher, even though coaxing the animals into restrainers becomes easier day-to-day.…”

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confidence: 99%

Exercising Restraint in Measuring Blood Pressure in Conscious Mice

Groß

Luft²

2003

Hypertension

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A rat's tail is a slender appendage on which the weight of so much research in hypertension hangs, yet blood pressure measurements recorded from it are usually taken for granted, often abused, but seldom discussed," observed Buang in an earlier commentary. 1 The same methodology has now been adapted to mice. Restraining the animals is a serious problem. A 7-day training period is recommended to accustom the animals to the restrainers. [2][3][4] Nevertheless, heart rates recorded while mice are in a restrainer are higher than those in the resting state. 3 Furthermore, blood pressures also appear to be higher, even though coaxing the animals into restrainers becomes easier day-to-day. 5 A blood pressure-elevating effect of restrainers has been observed in the rat. 6 Telemetric blood pressure and heart rate solves this problem. 6 We made telemetric measurements of blood pressure and heart rate on four 129Sv/J mice outfitted with telemetry as described earlier. 7 The purpose of our observations was to test the notion that "conditioning" might lessen the effects of restraint on blood pressure and heart rate. After an initial 120-minute control period, the mice were placed for 30 minutes in a 25-mm wide, 110-mm long lucite restrainer. Thereafter blood pressure and heart rate were recorded for an additional 120 minutes. We made daily recordings, 10 recordings for each mouse during 2 weeks. To judge the influence of restraint, we used the heart rate (HR) and the mean arterial pressure (MAP). In mice, tail-cuff pressure correlates well with MAP, according to earlier reports. 2,3 Data (meanϮSEM) were analyzed with the one-way ANOVA and t tests with the Bonferroni correction. The experimental protocol was approved by the local council on animal care, whose standards correspond to those of the American Physiological Society. Figure 1 shows HR and systolic (SBP) and diastolic blood pressures (DBP) from a representative mouse during the first restraint and the tenth restraint. The responses do not appear different. At the first restraint, SBP increased to 148 mm Hg, DBP to 113 mm Hg, and HR to 754 beats/ min. In the second week, at the tenth restraint, the responses to the restrainer were similar. Figure 2 shows that MAP measured under control conditions for 4 mice was stable throughout the 2-week recording period and averaged 102Ϯ8 mm Hg in the first week and 100Ϯ7 mm Hg in the second week. The corresponding basal HR values were 522Ϯ11 beats/min in the first week and 483Ϯ9 beats/min in the second week. No "conditioning" was observed for either MAP or HR when comparing the sessions of the first week with the sessions of the second week (PϭNS). Two hours after restraint, blood pressure and heart rate returned to basal levels in the mice.We conclude that blood pressure and heart rate increases are similar during restraining, independent of "conditioning" over 10 days. The data were convincing to the point that 4 mice were sufficient to illustrate the problem, so we did not study more. The results indicate that both blood pressu...

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Models of Experimental Hypertension in Mice

Cited by 156 publications

References 33 publications

Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression

Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression

Endostatin lowers blood pressure via nitric oxide and prevents hypertension associated with VEGF inhibition

Exercising Restraint in Measuring Blood Pressure in Conscious Mice

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