(Hypertension. 1996;28:1064-1069.)
© 1996 American Heart Association, Inc.
Articles |
Models of Experimental Hypertension in Mice
the Hypertension and Atherosclerosis Section of the Department of Medicine, Boston (Mass) University School of Medicine.
Correspondence to Haralambos Gavras, MD, Hypertension and Atherosclerosis Section, Boston University School of Medicine, 80 E Concord St, Boston, MA 02118.
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Abstract |
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Experimental models of hypertension in various animals are useful in the research of vasoactive mechanisms. Recombinant DNA technology has produced genetically engineered animals, mostly mice, useful in hypertension research. However, the development of hypertensive models in mice is fraught with technical difficulties. We describe here the successful development in mice of two common types of experimental hypertension: the renovascular two-kidney, one clip and mineralocorticoid deoxycorticosterone-salt models. By adapting technology previously used in rats, we succeeded in developing hypertension (defined as systolic pressures higher than 140 mm Hg) in more than 50% of mice so treated. We also adapted the methodology for indirect tail-cuff blood pressure measurements as well as for direct intra-arterial monitoring of blood pressure in conscious, freely moving mice. Application of these techniques in transgenic or gene knockout mice with altered vasoactive hormones or receptors should allow elucidation of the role of the target gene products in various types of hypertension.
Key Words: hypertension, renovascular • hypertension, mineralocorticoid • deoxycorticosterone • blood pressure monitoring • mice
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Introduction |
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Various experimental animal models have been used in the research of the pathophysiology of hypertension. Traditionally, one of the preferred approaches has been to create in rats or larger animals hypertension mimicking known human pathology by surgical manipulation, eg, renal artery stenosis, partial ablation of renal mass, mineralocorticoid excess, etc. These animal models are then treated with pharmacological probes selectively affecting a vasoactive mechanism (such as agonists or antagonists of specific hormone receptors) for evaluation of the role of the targeted mechanism in the type of hypertension being studied.
Recent advances in recombinant DNA technology have permitted the creation of genetically altered animals in which the genes controlling certain hormones or receptors have been engineered to overexpress or disrupt the production of the relevant hormone or receptor protein. Although transgenic and gene knockout techniques have been applied to a few species, mice are by far the most successfully and widely used.1 Mice genetically altered with regard to the gene controlling a specific vasoactive mechanism are ideally suited to the evaluation of the role of that particular mechanism in the development or maintenance of certain types of hypertension. However, as has been pointed out by Chien,2 one of the preeminent experts in the field, the skills required to generate gene-targeted mice are different from the expertise necessary to quantitatively monitor a complex physiological phenotype such as a cardiovascular disease. Furthermore, the development of the classic animal models of experimental hypertension—renovascular, mineralocorticoid, etc.—in mice is a technically daunting task, as it requires adaptation of surgical and other manipulations from the 300-g rat to the 15- to 30-g mouse with its diminutive organs and blood vessels.
In this report, we describe the successful development of renovascular and deoxycorticosterone (DOC)-salt hypertension, as well as methodology for continuous blood pressure (BP) monitoring in unanesthetized, freely moving mice.
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Methods |
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Male Swiss Webster mice weighing between 15 and 32 g (Charles River Breeding Laboratories, Inc, Wilmington, Mass) were used in all experiments. They were housed in a temperature- and humidity-controlled room with a 12-hour light/dark cycle. All mice were allowed free access to regular food (Rodent Laboratory Chow, Purina Mills) and tap water. For mice used for the DOC experiments, drinking water was replaced with 1% NaCl. All experiments were conducted in accordance with the guidelines for the care and use of animals approved by the Boston University Medical Center.
Renovascular Hypertension
Mice were anesthetized with 50 mg/kg body wt pentobarbital IP and placed on a 37°C heated surgical surface. A midline incision was made in the abdominal cavity and a silver clip placed around the right renal artery. The clip was made from pure silver ribbon 0.25 mm thick by 1.5 mm wide. With a dissecting microscope, a slit (1 mm long) was cut into the ribbon with a 0.051-mm-thick metal gauge and expanded to various widths ranging between 0.051 and 0.127 mm (after testing each size in two mice, we opted eventually for the 0.076-mm width). With the slit centered, the silver ribbon was cut into a rectangle 1.5x1 mm. The edges were rounded with a blade. Mice were sutured and returned to a warm cage until they fully recovered. Control mice were sham operated.
DOC-Salt Hypertension
Mice were anesthetized as above. A flank incision was made to expose the left kidney, which was ligated and removed. The incision was sutured. A 50-mg DOC pellet was implanted subcutaneously in the abdominal area. The mice were allowed to recover in a warm cage. Subsequently, they were given regular rodent chow and a 1% NaCl solution as drinking water. Control mice were uninephrectomized without having a DOC pellet implanted and were given tap water to drink.
Indirect BP was determined with a pulse amplifier (model 29) and computerized BP monitor (model 31, IITC, Inc). This system measures systolic BP photoelectrically by recording the cuff pressure at which the interrupted blood flow returns to the tail. Training the mice for tail-cuff BP measurements was necessary to reduce the stress associated with the BP measurements and hence reduce the variability of BP with successive measurements. Training consisted of six sessions over 3 days. On day 1, mice were introduced into the plastic restrainer for 5 minutes per session. The tail cuff was inflated five times in quick succession. By day 3, the training was extended to 10 minutes per session. The effect of training was to reduce the standard deviation around the mean BP. At the end of the training sessions, mice were ready for BP recording. They were restrained by being placed into a cylindrical restrainer 2.5 cm in diameter and 10 cm long (model 84, IITC, Inc) modified by insertion of a conical metal insert into one end of the restrainer to cover the mouse's head. This modification greatly improved the reliability of BP readings by reducing stress and movement. For better detection of tail pulse, the tail artery was dilated by placement of the restrained mouse into a thermostatically controlled Lucite box (16 cm wide, 11 cm high, 30 cm long), heated at 33° to 34°C, for 2 to 5 minutes before BP measurement was started. Tail pulse was detected by passage of the tail through a tail-cuff sensor (model B60-1/4) attached to the amplifier. The tail was immobilized and heat transfer improved by passage of the tail through a narrow glass cylinder. BP measurements were started by manual inflation of the tail cuff to greater than 200 mm Hg and release of the pressure. The amplified pulse was recorded and stored in a computer via an analog/digital board. The computer program provides two tracings that start and stop at the same time. The upper trace channel plots cuff pressure, which is calibrated to 300 mm Hg at full scale. The tracing rises sharply when pressure is applied to the tail cuff and falls off gradually during the 15 to 20 seconds of the test. The lower trace channel monitors pulse, with fluctuations about the center line suddenly appearing at the onset of pulsations (Fig 1
). The first onset of pulse is taken as the systolic BP. Initiation of pulse pressure was determined when the baseline amplitude increased by 8 of 300 of the set maximal inflated cuff pressures; maximal inflation was set at 200 mm Hg. BP readings were considered to be successful if the mouse did not move and a clear initial pulse could be seen. Ten tail-cuff measurements were made in a session. The BP for the session was accepted as the average of four BP readings that were within 5 mm Hg or the average of 10 readings that were within 8 mm Hg. We routinely show a difference of less than 3 mm Hg in average BP calculated by these two different sets of criteria during one session.
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BP measurements were done once or twice per week for 4 weeks. After the 4th week of tail-cuff measurements, intra-arterial BP was measured. Mice were anesthetized with 50 mg/kg body wt pentobarbital IP. The iliac artery was catheterized with a catheter fashioned from PE-50 tubing flushed with approximately 50 µL of 50 IU/mL heparin in 0.9% saline. The catheter was made pliable by heating over a small hot plate and pulling the soft tubing to an external diameter of 0.22 to 0.25 mm. We found that catheter construction is very important. Most catheter failures were due to clots or excessive bleeding caused by excessive manipulation of the catheter tip. These problems can be avoided by constructing catheters with long, gradual tapers of about 4 to 5 cm in length. Catheters made with long tapers were more pliable, which made it easier to control and reduce clots. This type of catheter construction reduced our catheter failure rate from 40% to 10%. The catheter was placed in the left iliac artery and threaded to the level of the junction with the abdominal aorta. The catheter was tunneled subcutaneously to exit the mouse at the nape. Approximately 1 cm of the catheter was exteriorized and sealed with heat. We found that this catheter length prevented mice from chewing the catheter.
After surgery, mice were allowed to recover and were housed overnight in separate cages with food and water. The next day, the distal end of the PE-50 line was connected to a pressure transducer attached to the recorder (model 220S, Gould Inc). BP was recorded for 1 hour. By 30 minutes, the mice were resting quietly on their bedding and BP readings were stable. BP readings were averaged over the last 15 to 30 minutes of each period. Mean arterial pressure (MAP) was determined by setting the recorder to the average setting. A typical BP pressure recording is shown in Fig 2.
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The success rate of this procedure was as follows: We attempted 28 iliac catheterization procedures, of which 16 (57%) were successful. We had 7 catheter failures (25%) caused by clots. As mentioned above, we were able to reduce our catheter failure to 10% by modifying the tapers of our catheters. Two initial mice (7%) were killed because of excessive bleeding. Subsequently, losses caused by bleeding were eliminated probably because of catheter improvements. Two mice (7%) bit their catheters during recovery from surgery. By reducing the exposed catheter to 1 cm, we were able to eliminate this problem. One mouse (4%) died overnight.
In some renovascular mice, after 1 hour of intra-arterial BP recording, a bolus of 50 mg/kg of the angiotensin II antagonist losartan (Merck Co) was given through the arterial line. BP was followed for an additional 2 hours after the losartan bolus. At the end of the experiments, mice randomly selected from the various experimental groups were killed and their organs removed and weighed.
Results are reported as mean±SE. Comparisons were made by Student's t test or ANOVA for repeated measures, as appropriate. Differences were considered to be significant at a value of P<.05. Comparison of indirect tail-cuff systolic BP and direct intra-arterial MAP was made by reverse regression and reported as the slope, with its standard error and the intercept. In this calculation, y is predicted from x.
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Results |
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Group 1
We used the first group of mice (n=5) to test the consistency and reliability of indirect BP measurements. Systolic BP was measured once weekly for 2 weeks; the results are shown in Table 1
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Group 2
We used group 2 mice (n=10) to try various clip sizes to determine which was most successful in elevating BP at 2 weeks, thus promising to produce a model of renovascular hypertension. In constructing the renal artery clip, we emphasized designing a shape and slit size that would facilitate placing the clip around the renal artery with ease and without totally occluding the artery. With the preliminary group, the most consistent high BPs were from mice with a clip size of 0.076 mm. Clips with larger slit sizes, 0.127 and 0.102 mm, yielded BPs in the normal range. A renal clip size of 0.061 mm yielded high BPs, but the kidney appeared smaller and more ischemic (white) than in mice with a clip size of 0.076 mm. Mice with a renal clip size of 0.051 mm had BPs in the normal range; they also had a very small white kidney, which was difficult to find and had presumably lost its secretory capacity. Table 2 lists systolic BP 2 weeks after clip placement in two mice for each clip size.
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Groups 3, 4, and 5
On the basis of the previous findings, we chose to use the 0.076-mm clip on group 3 (n=15) and the 0.061-mm clip on group 4 (n=7). We designated a minimum of 140 mm Hg systolic BP as the criterion for established renovascular hypertension after 4 weeks. By the end of the 3rd week, 8 of 15 mice in group 3 and 2 of 7 mice in group 4 had become hypertensive, with systolic BP greater than 140 mm Hg. Table 3 shows the weekly systolic BP of these groups and their control, group 5.
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In four of these mice, treatment with intra-arterial losartan resulted in a fall of MAP from 148±4 to 116±7 mm Hg (P<.02) at 5 minutes after injection. After 2 hours, MAP was still depressed (118±2 mm Hg).
Groups 6 and 7
DOC-salt hypertension was induced in group 6 mice (n=7), with group 7 (n=6) serving as controls (uninephrectomized but not treated with DOC pellet or 1% saline as drinking water). Their data are shown in Table 4. At 4 weeks after intervention, four of seven mice in group 6 were hypertensive, with systolic BP greater than 140 mm Hg, whereas none in group 7 had systolic BP higher than 111 mm Hg.
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Relationship Between Indirect and Direct BP
In 16 mice randomly selected from various groups, we compared indirect (tail-cuff) systolic BP and direct (intra-arterial) MAP. The close correlation (r=.876, P<.001) of the results, shown in Fig 3, confirms the accuracy of BP measurement by both methods. When direct MAP was plotted against tail-cuff systolic BP, the reverse regression line revealed a slope of 0.83±0.167 and an intercept of 16.1.
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indicates renovascular hypertensive mice; 
, "renovascular" sham-operated mice; 
, deoxycorticosterone-salt hypertensive mice; and 
, uninephrectomized control mice.
Organ Weights
At the end of the experiments, randomly selected mice from each experimental group were weighed and had their hearts and kidneys removed and weighed. Wet weights are shown in Table 5 as absolute weights and relative to body weight. As expected, the clipped right kidney of the renovascular hypertensive mice was much smaller than that of the normotensive sham-operated controls, whereas the contralateral kidney was enlarged. In the hypertensive DOC-salt mice, the remaining right kidney was grossly enlarged compared with the normal kidney and was significantly larger than that of the normotensive uninephrectomized DOC controls, whose remaining kidney was also larger than normal, as anticipated. Surprisingly, neither of the two hypertensive groups had developed cardiomegaly. The average body weight did not differ between groups (29±1.6 g in renovascular mice, 26±0.7 in their controls, 26±0.7 in DOC-salt mice, and 26±0.6 in DOC controls).
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Discussion |
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In this report, we describe the development of two common types of experimental hypertension in mice: renovascular via a two-kidney, one clip maneuver, and mineralocorticoid via uninephrectomy and DOC-salt. Both models have been used extensively for the study of the mechanisms, pathophysiology, and therapeutic modalities of hypertension that have then been extrapolated and applied to humans. The first experimental model of renovascular hypertension, developed by Goldblatt et al in 1934,3 demonstrated that renal ischemia is the cause of this syndrome. Subsequent studies were mostly conducted in rats to explore, among other things, the early and late biochemical and hormonal changes4 and the reciprocal relationship between salt loading and renin oversecretion5 6 in renovascular hypertension. Likewise, the DOC-salt model in rats was used to describe the natural history of malignant hypertension and the biochemical and hormonal characteristics of each stage of the disease.7 8 Several of these studies relied on the responses produced by pharmacological agonists and antagonists to define the contribution of various hormone/receptor systems to the particular type of hypertension.
When the technology needed to produce transgenic animals became available, one of its first applications was to transfect the Ren-2 mouse renin gene into Sprague-Dawley rats. These rats developed a severe form of renin-dependent hypertension and were used for the study of the mechanisms and consequences of this monogenic hypertension.9 10 11 However, to date, the study of the role of particular genes in BP regulation has used mice far more extensively, especially because transgenic techniques are easier to apply in mice. Tables 6 and 7 summarize the findings of many transgenic mouse models relevant to hypertension. These models have shown the importance of genes encoding components of the renin-angiotensin system as well as genes encoding other vasoactive substances related to BP control. Interestingly, different groups have obtained different results with regard to the effects of several of these genes. For example, the angiotensin II type 2 receptor (AT2R) knockout has no effect on baseline BP in one knockout model22 but increases BP in another,23 whereas both AT2R knockouts exhibit increased vasopressor responses to angiotensin II. Apparently, different animal strains were used in generating each of these models, and strain-specific differences may influence the phenotype.30 Thus, the importance of a gene in BP regulation may not be uncovered unless the model is tested by pharmacophysiological probes, such as angiotensin II in the above models. In addition, there are many other transgenic models—such as those overexpressing ß2-adrenoceptors,31 knockout mice with disrupted genes encoding for 
2-adrenoceptor subtypes,32 or the bradykinin B2 receptor—whose physiological implications in BP regulation are still being explored. Other transgenic models, which are being created and reported continually, may have important cardiovascular implications. Inbred mouse models mimicking human essential hypertension33 or non–insulin-dependent diabetes mellitus with hypertension34 have also been described. At this point, there is a need to generate in mice the experimental models in which the pathophysiological profile and prevailing mechanisms of hypertension have been extensively studied in larger animals with the use of classic pharmacological probes. It will then be possible to study these models in genetically altered mice to better define the role of the targeted gene product in controlling BP.
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The obstacles to successfully duplicating the known experimental rat models in mice are to accurately assess BP by direct and indirect methods35 and to adapt the standard surgical and pharmacological techniques. In this report, we have demonstrated that BP measurements by both the indirect tail-cuff and direct intra-arterial catheter methods are reliable and reproducible with minimal variability, in accordance with the results reported recently by another laboratory.35 The close correlation of the results obtained in the same mice by the two methods indicates that their accuracy is at least as good as that reported for rats.36 We have also described how we approached the technical aspects (eg, designing appropriately sized renal artery clips) to produce these models. In both renovascular and DOC-salt mice, we were able to induce significant elevations in systolic BP to more than 140 mm Hg in about half of the animals. Another team has also reported the development of DOC-salt hypertension in mice37 ; as with our mice, the average systolic BP in their groups was barely higher than 140 mm Hg. By contrast, in renovascular or DOC-salt hypertensive rats, systolic BP at 4 weeks is in the range of 200 mm Hg.4 5 6 7 8 Evidently, the magnitude of BP rise and the rate of success in mice are still less than those in rats. It is notable that the strains of inbred genetically hypertensive mice found so far also tend to have a lesser BP elevation than that seen in spontaneously hypertensive rats.33 The kidney sizes in each experimental group were found to be appropriately changed, as expected, from each procedure, further corroborating the fact that the respective manipulations were successful. In this respect, mice appear to resemble hypertensive rabbit models, which develop the changes of severe hypertension even though they attain only relatively modest BP levels.38
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Acknowledgments |
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This work was supported by National Institutes of Health grant 1 P50 HL-55001.
Received May 28, 1996; first decision June 4, 1996; accepted July 8, 1996.
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J. E. Wagenseil, R. H. Knutsen, D. Y. Li, and R. P. Mecham Elastin-insufficient mice show normal cardiovascular remodeling in 2K1C hypertension despite higher baseline pressure and unique cardiovascular architecture Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H574 - H582. [Abstract] [Full Text] [PDF]
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G. Gavazzi, C. Deffert, C. Trocme, M. Schappi, F. R. Herrmann, and K.-H. Krause NOX1 Deficiency Protects From Aortic Dissection in Response to Angiotensin II Hypertension, July 1, 2007; 50(1): 189 - 196. [Abstract] [Full Text] [PDF]
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L. Ding, A. Chapman, R. Boyd, and H. D. Wang ERK activation contributes to regulation of spontaneous contractile tone via superoxide anion in isolated rat aorta of angiotensin II-induced hypertension Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2997 - H3005. [Abstract] [Full Text] [PDF]
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 N. P. L. Rolim, A. Medeiros, K. T. Rosa, K. C. Mattos, M. C. Irigoyen, E. M. Krieger, J. E. Krieger, C. E. Negrao, and P. C. Brum Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure Physiol Genomics, May 11, 2007; 29(3): 246 - 252. [Abstract] [Full Text] [PDF]
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T.-A. S. Duhaney, L. Cui, M. K. Rude, N. K. Lebrasseur, S. Ngoy, D. S. De Silva, D. A. Siwik, R. Liao, and F. Sam Peroxisome Proliferator-Activated Receptor {alpha}-Independent Actions of Fenofibrate Exacerbates Left Ventricular Dilation and Fibrosis in Chronic Pressure Overload Hypertension, May 1, 2007; 49(5): 1084 - 1094. [Abstract] [Full Text] [PDF]
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L. V. d'Uscio, L. A. Smith, A. V. Santhanam, D. Richardson, K. A. Nath, and Z. S. Katusic Essential Role of Endothelial Nitric Oxide Synthase in Vascular Effects of Erythropoietin Hypertension, May 1, 2007; 49(5): 1142 - 1148. [Abstract] [Full Text] [PDF]
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 G. C. Kane, A. Behfar, R. B. Dyer, D. F. O'Cochlain, X.-K. Liu, D. M. Hodgson, S. Reyes, T. Miki, S. Seino, and A. Terzic KCNJ11 gene knockout of the Kir6.2 KATP channel causes maladaptive remodeling and heart failure in hypertension Hum. Mol. Genet., August 1, 2006; 15(15): 2285 - 2297. [Abstract] [Full Text] [PDF]
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 A. R. Karuri, Y. Huang, S. Bodreddigari, C. H. Sutter, B. D. Roebuck, T. W. Kensler, and T. R. Sutter 3H-1,2-Dithiole-3-thione Targets Nuclear Factor {kappa}B to Block Expression of Inducible Nitric-Oxide Synthase, Prevents Hypotension, and Improves Survival in Endotoxemic Rats J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 61 - 67. [Abstract] [Full Text] [PDF]
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 R. Matsui, S. Xu, K. A. Maitland, R. Mastroianni, J. A. Leopold, D. E. Handy, J. Loscalzo, and R. A. Cohen Glucose-6-Phosphate Dehydrogenase Deficiency Decreases Vascular Superoxide and Atherosclerotic Lesions in Apolipoprotein E-/- Mice Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 910 - 916. [Abstract] [Full Text] [PDF]
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 S. Xu, B. Jiang, K. A. Maitland, H. Bayat, J. Gu, J. L. Nadler, S. Corda, G. Lavielle, T. J. Verbeuren, A. Zuccollo, et al. The Thromboxane Receptor Antagonist S18886 Attenuates Renal Oxidant Stress and Proteinuria in Diabetic Apolipoprotein E-Deficient Mice Diabetes, January 1, 2006; 55(1): 110 - 119. [Abstract] [Full Text] [PDF]
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 A. Dikalova, R. Clempus, B. Lassegue, G. Cheng, J. McCoy, S. Dikalov, A. S. Martin, A. Lyle, D. S. Weber, D. Weiss, et al. Nox1 Overexpression Potentiates Angiotensin II-Induced Hypertension and Vascular Smooth Muscle Hypertrophy in Transgenic Mice Circulation, October 25, 2005; 112(17): 2668 - 2676. [Abstract] [Full Text] [PDF]
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R. M.P. Arruda, V. A. Peotta, S. S. Meyrelles, and E. C. Vasquez Evaluation of Vascular Function in Apolipoprotein E Knockout Mice With Angiotensin-Dependent Renovascular Hypertension Hypertension, October 1, 2005; 46(4): 932 - 936. [Abstract] [Full Text] [PDF]
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R. Matsui, S. Xu, K. A. Maitland, A. Hayes, J. A. Leopold, D. E. Handy, J. Loscalzo, and R. A. Cohen Glucose-6 Phosphate Dehydrogenase Deficiency Decreases the Vascular Response to Angiotensin II Circulation, July 12, 2005; 112(2): 257 - 263. [Abstract] [Full Text] [PDF]
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M. Dworschak, L. V. d'Uscio, D. Breukelmann, and J. D. Hannon Increased tolerance to hypoxic metabolic inhibition and reoxygenation of cardiomyocytes from apolipoprotein E-deficient mice Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H160 - H167. [Abstract] [Full Text] [PDF]
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 C. Hosoda, T.-a. Koshimizu, A. Tanoue, Y. Nasa, R. Oikawa, T. Tomabechi, S. Fukuda, H. Shinoura, S. Oshikawa, S. Takeo, et al. Two {alpha}1-Adrenergic Receptor Subtypes Regulating the Vasopressor Response Have Differential Roles in Blood Pressure Regulation Mol. Pharmacol., March 1, 2005; 67(3): 912 - 922. [Abstract] [Full Text] [PDF]
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F. Schwartz, A. Duka, I. Duka, J. Cui, and H. Gavras Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1957 - H1966. [Abstract] [Full Text] [PDF]
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 E. Lazartigues, A. J. Lawrence, F. S. Lamb, and R. L. Davisson Renovascular Hypertension in Mice With Brain-Selective Overexpression of AT1a Receptors Is Buffered by Increased Nitric Oxide Production in the Periphery Circ. Res., September 3, 2004; 95(5): 523 - 531. [Abstract] [Full Text] [PDF]
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S. E. Whitesall, J. B. Hoff, A. P. Vollmer, and L. G. D'Alecy Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2408 - H2415. [Abstract] [Full Text] [PDF]
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F. Schwartz, A. Duka, E. Triantafyllidi, C. Johns, I. Duka, J. Cui, and H. Gavras Serial analysis of gene expression in mouse kidney following angiotensin II administration Physiol Genomics, December 16, 2003; 16(1): 90 - 98. [Abstract] [Full Text] [PDF]
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I. Duka, A. Duka, E. Kintsurashvili, C. Johns, I. Gavras, and H. Gavras Mechanisms Mediating the Vasoactive Effects of the B1 Receptors of Bradykinin Hypertension, November 1, 2003; 42(5): 1021 - 1025. [Abstract] [Full Text] [PDF]
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V. Walsh, L. Somody, A. Farrell, B. Zhang, J. Brown, C. Pritchard, M. Vincent, and N. J. Samani Analysis of the Role of the SA Gene in Blood Pressure Regulation by Gene Targeting Hypertension, June 1, 2003; 41(6): 1212 - 1218. [Abstract] [Full Text] [PDF]
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V. Gross and F. C. Luft Exercising Restraint in Measuring Blood Pressure in Conscious Mice Hypertension, April 1, 2003; 41(4): 879 - 881. [Full Text] [PDF]
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P. C. Brum, J. Kosek, A. Patterson, D. Bernstein, and B. Kobilka Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1838 - H1845. [Abstract] [Full Text] [PDF]
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 Q. Wang, E. Hummler, J. Nussberger, S. Clement, G. Gabbiani, H. R. Brunner, and M. Burnier Blood Pressure, Cardiac, and Renal Responses to Salt and Deoxycorticosterone Acetate in Mice: Role of Renin Genes J. Am. Soc. Nephrol., June 1, 2002; 13(6): 1509 - 1516. [Abstract] [Full Text] [PDF]
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B. J. A. Janssen and J. F. M. Smits Autonomic control of blood pressure in mice: basic physiology and effects of genetic modification Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1545 - R1564. [Abstract] [Full Text] [PDF]
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E. Kintsurashvili, I. Gavras, C. Johns, and H. Gavras Effects of Antisense Oligodeoxynucleotide Targeting of the {alpha}2B-Adrenergic Receptor Messenger RNA in the Central Nervous System Hypertension, November 1, 2001; 38(5): 1075 - 1080. [Abstract] [Full Text] [PDF]
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E. Kintsurashvili, I. Duka, I. Gavras, C. Johns, D. Farmakiotis, and H. Gavras Effects of ANG II on bradykinin receptor gene expression in cardiomyocytes and vascular smooth muscle cells Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1778 - H1783. [Abstract] [Full Text] [PDF]
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V. A. Peotta, E. C. Vasquez, and S. S. Meyrelles Cardiovascular Neural Reflexes in L-NAME-Induced Hypertension in Mice Hypertension, September 1, 2001; 38(3): 555 - 559. [Abstract] [Full Text] [PDF]
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I. Duka, E. Kintsurashvili, I. Gavras, C. Johns, M. Bresnahan, and H. Gavras Vasoactive Potential of the B1 Bradykinin Receptor in Normotension and Hypertension Circ. Res., February 16, 2001; 88(3): 275 - 281. [Abstract] [Full Text] [PDF]
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 P. Meneton, I. Ichikawa, T. Inagami, and J. Schnermann Renal physiology of the mouse Am J Physiol Renal Physiol, March 1, 2000; 278(3): F339 - F351. [Abstract] [Full Text] [PDF]
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B. J. A. Janssen, P. J. A. Leenders, and J. F. M. Smits Short-term and long-term blood pressure and heart rate variability in the mouse Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2000; 278(1): R215 - R225. [Abstract] [Full Text] [PDF]
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K. P. Makaritsis, C. Johns, I. Gavras, J. D. Altman, D. E. Handy, M. R. Bresnahan, and H. Gavras Sympathoinhibitory Function of the {alpha}2A-Adrenergic Receptor Subtype Hypertension, September 1, 1999; 34(3): 403 - 407. [Abstract] [Full Text] [PDF]
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K. P. Makaritsis, D. E. Handy, C. Johns, B. Kobilka, I. Gavras, and H. Gavras Role of the {alpha}2B-Adrenergic Receptor in the Development of Salt-Induced Hypertension Hypertension, January 1, 1999; 33(1): 14 - 17. [Abstract] [Full Text] [PDF]
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P. Madeddu, A. F. Milia, M. B. Salis, L. Gaspa, W. Gross, A. Lippoldt, and C. Emanueli Renovascular Hypertension in Bradykinin B2-Receptor Knockout Mice Hypertension, September 1, 1998; 32(3): 503 - 509. [Abstract] [Full Text] [PDF]
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D. L. Mattson Long-term measurement of arterial blood pressure in conscious mice Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R564 - R570. [Abstract] [Full Text] [PDF]
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F. Franco, S. K. Dubois, R. M. Peshock, and R. V. Shohet Magnetic resonance imaging accurately estimates LV mass in a transgenic mouse model of cardiac hypertrophy Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H679 - H683. [Abstract] [Full Text] [PDF]
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H. D. Wang, D. G. Johns, S. Xu, and R. A. Cohen Role of superoxide anion in regulating pressor and vascular hypertrophic response to angiotensin II Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1697 - H1702. [Abstract] [Full Text] [PDF]
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H. D. Wang, S. Xu, D. G. Johns, Y. Du, M. T. Quinn, A. J. Cayatte, and R. A. Cohen Role of NADPH Oxidase in the Vascular Hypertrophic and Oxidative Stress Response to Angiotensin II in Mice Circ. Res., May 9, 2001; 88(9): 947 - 953. [Abstract] [Full Text] [PDF]
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