Characterization of blood pressure and morphological traits in cardiovascular-related organs in 13 different inbred mouse strains

2004 ◽  
Vol 97 (1) ◽  
pp. 369-376 ◽  
Author(s):  
Christian F. Deschepper ◽  
Jean L. Olson ◽  
Melissa Otis ◽  
Nicole Gallo-Payet

To better understand the contributions of various genetic backgrounds to complex quantitative phenotypes, we have measured several quantitative traits of cardiovascular interest [i.e., systolic blood pressure, weight (corrected by body weight) of several cardiac compartments and adrenals and kidneys, and histological correlates for kidneys and adrenals] in male and female mice from 13 different inbred strains. We selected strains so that each major genealogical group would be represented and to conform to priorities set by the Mouse Phenome Database project. Interstrain comparisons of phenotypes made it possible to identify strains that displayed values that belonged to either the low or the high end of the interstrain variance for quantitative traits, such as systolic blood pressure, body weight, left ventricular weight, and/or adrenocortical structure. For instance, both male and female C3H/HeJ and A/J mice displayed either low systolic blood pressure or low cardiac ventricular mass, respectively, and male C57BL6/J displayed low adrenal weight. Likewise, intersex comparisons made it possible to identify phenotypic values that were sexually dimorphic for some of the same traits. For instance, female AKR/J mice had relatively higher body weight and systolic blood pressure values than their male counterparts, perhaps constituting an animal model of the metabolic X syndrome. These strain- and sex-specific features will be of value both for future genetic and/or developmental studies and for the development of new animal models that will help in the generation of mechanistic hypotheses. All data have been deposited to the Mouse Phenome Database for future integration with the Mouse Genome Database and can be further analyzed and compared with tools available on the site.

Author(s):  
Crystal H Gergye ◽  
Yixuan Zhao ◽  
Reneé H Moore ◽  
Vanessa K Lee

Intraperitoneal (IP) injection is a common route of anesthetic administration in mice. Ketamine-xylazine (KX) anesthesia is one of the most widely used IP protocols, but has limitations. Etomidate is an alternative to ketamine that has been used in both human and veterinary medicine yet has not been widely studied in mice. The purpose of this study was to evaluate etomidate-xylazine (EX) anesthesia as an alternative to KX. We hypothesized that EX would be as safe and effective as KX, with both sex- and strain-dependent differences. Male and female Crl:CD1(ICR), C57BL/6NCrl, BALB/cJ and NU/J mice were given a single IP dose of ketamine 100 mg/kg and xylazine 10 mg/kg or etomidate 20 mg/kg and xylazine 10 mg/kg. Sedation times were similar between KX and EX, with CD1 mice exhibiting shorter sedation times. Surgical anesthesia was achieved in 44% of EX mice, compared with 4% of KX mice. C57BL/6NCrl mice were significantly more likely to achieve surgical anesthesia when given EX (94%) or KX (18%) than were other strains. In all strains except C57BL/6NCrl mice, females were more likely to reach surgical anesthesia than males. Several mice experienced an adverse hyperexcitement response during induction, with BALB/cJ (79%) and NU/J (87%) mice given EX significantly more likely than other strains to experience hyperexcitement. EX and KX protocols had no overall differences in lowest respiration rate, lowest systolic blood pressure, lowest rectal temperature, or levels of acidosis, although the lowest heart rates were significantly higher with EX, indicating that EX and KX have similar safety profiles. Thus, EX and KX administration were associated with several significant physiologic differences when comparing sexes or individual strains. Our results indicate that EX is an equally effective sedative and a more effective surgical anesthetic than KX; however, EX is only recommended for invasive procedures in C57BL/6 mice due to the high rate of hyper-excitement and inconsistent surgical depth seen in other strains. Further study is needed to optimize EX for use in multiple mouse strains.


2009 ◽  
Vol 116 (3) ◽  
pp. 249-255 ◽  
Author(s):  
Junhua He ◽  
Yunfei Bian ◽  
Fen Gao ◽  
Maolian Li ◽  
Ling Qiu ◽  
...  

The purpose of the present study was to investigate the effects on blood pressure and myocardial hypertrophy in SHRs (spontaneously hypertensive rats) of RNAi (RNA interference) targeting ACE (angiotensin-converting enzyme). SHRs were treated with normal saline as vehicle controls, with Ad5-EGFP as vector controls, and with recombinant adenoviral vectors Ad5-EGFP-ACE-shRNA, carrying shRNA (small hairpin RNA) for ACE as ACE-RNAi. WKY (Wistar–Kyoto) rats were used as normotensive controls treated with normal saline. The systolic blood pressure of the caudal artery was recorded. Serum levels of ACE and AngII (angiotensin II) were determined using ELISA. ACE mRNA and protein levels were determined in aorta, myocardium, kidney and lung. On day 32 of the experiment, the heart was pathologically examined. The ratios of heart weight/body weight and left ventricular weight/body weight were calculated. The serum concentration of ACE was lower in ACE-RNAi rats (16.37±3.90 ng/ml) compared with vehicle controls and vector controls (48.26±1.50 ng/ml and 46.67±2.82 ng/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (14.88±3.15 ng/ml; P>0.05). The serum concentration of AngII was also significantly lower in ACE-RNAi rats (18.24±3.69 pg/ml) compared with vehicle controls and vector controls (46.21±5.06 pg/ml and 44.93±4.12 pg/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (16.06±3.11 pg/ml; P>0.05). The expression of ACE mRNA and ACE protein were significantly reduced in the myocardium, aorta, kidney and lung in ACE-RNAi rats compared with that in vehicle controls and in vector controls (all P<0.05). ACE-RNAi treatment resulted in a reduction in systolic blood pressure by 22±3 mmHg and the ACE-RNAi-induced reduction lasted for more than 14 days. In contrast, blood pressure was continuously increased in the vehicle controls as well as in the vector controls. The ratios of heart weight/body weight and left ventricular weight/body weight were significantly lower in ACE-RNAi rats (3.12±0.23 mg/g and 2.24±0.19 mg/g) compared with the vehicle controls (4.29±0.24 mg/g and 3.21±0.13 mg/g; P<0.05) and the vector controls (4.43±0.19 mg/g and 3.13±0.12 mg/g; P<0.05). The conclusion of the present study is that ACE-silencing had significant antihypertensive effects and reversed hypertensive-induced cardiac hypertrophy in SHRs, and therefore RNAi might be a new strategy in controlling hypertension.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chao-Sheng Lo ◽  
Kana N. Miyata ◽  
Shuiling Zhao ◽  
Anindya Ghosh ◽  
Shiao-Ying Chang ◽  
...  

Abstract We reported previously that overexpression of heterogeneous nuclear ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.


2017 ◽  
Vol 122 (2) ◽  
pp. 223-229 ◽  
Author(s):  
Peter M. van Brussel ◽  
Bas van den Bogaard ◽  
Barbara A. de Weijer ◽  
Jasper Truijen ◽  
C.T. Paul Krediet ◽  
...  

Blood pressure (BP) decreases in the first weeks after Roux-and-Y gastric bypass surgery. Yet the pathophysiology of the BP-lowering effects observed after gastric bypass surgery is incompletely understood. We evaluated BP, systemic hemodynamics, and baroreflex sensitivity in 15 obese women[mean age 42 ± 7 standard deviation (SD) yr, body mass index 45 ± 6 kg/m2] 2 wk before and 6 wk following Roux-and-Y gastric bypass surgery. Six weeks after gastric bypass surgery, mean body weight decreased by 13 ± 5 kg (10%, P < 0.001). Office BP decreased from 137 ± 10/86 ± 6 to 128 ± 12/81 ± 9 mmHg ( P < 0.001, P < 0.01), while daytime ambulatory BP decreased from 128 ± 14/80 ± 9 to 114 ± 10/73 ± 6 mmHg ( P = 0.01, P = 0.05), whereas nighttime BP decreased from 111 ± 13/66 ± 7 to 102 ± 9/62 ± 7 mmHg ( P = 0.04, P < 0.01). The decrease in BP was associated with a 1.6 ± 1.2 l/min (20%, P < 0.01) decrease in cardiac output (CO), while systemic vascular resistance increased (153 ± 189 dyn·s·cm−5, 15%, P < 0.01). The maximal ascending slope in systolic blood pressure decreased (192 mmHg/s, 19%, P = 0.01), suggesting a reduction in left ventricular contractility. Baroreflex sensitivity increased from 9.0 [6.4–14.3] to 13.8 [8.5–19.0] ms/mmHg (median [interquartile range]; P < 0.01) and was inversely correlated with the reductions in heart rate ( R = −0.64, P = 0.02) and CO ( R = −0.61, P = 0.03). In contrast, changes in body weight were not correlated with changes in either BP or CO. The BP reduction following Roux-and-Y gastric bypass surgery is correlated with a decrease in CO independent of changes in body weight. The contribution of heart rate to the reduction in CO together with enhanced baroreflex sensitivity suggests a shift toward increased parasympathetic cardiovascular control. NEW & NOTEWORTHY The reason for the decrease in blood pressure (BP) in the first weeks after gastric bypass surgery remains to be elucidated. We show that the reduction in BP following surgery is caused by a decrease in cardiac output. In addition, the maximal ascending slope in systolic blood pressure decreased suggesting a reduction in left ventricular contractility and cardiac workload. These findings help to understand the physiological changes following gastric bypass surgery and are relevant in light of the increased risk of heart failure in these patients.


1963 ◽  
Vol 42 (6) ◽  
pp. 1465-1466 ◽  
Author(s):  
E.L. Nichols ◽  
D.K. Hotchkiss ◽  
S.L. Balloun

1983 ◽  
Vol 245 (5) ◽  
pp. F615-F621 ◽  
Author(s):  
R. L. Woods ◽  
C. I. Johnston

Normal Long-Evans rats, when dehydrated for up to 72 h, have a progressive rise in plasma vasopressin that is associated with a fall in body weight and urine volume, a rise in plasma and urine osmolality, and the maintenance of normal systolic blood pressure. In contrast, Brattleboro diabetes insipidus rats, genetically deficient in vasopressin, when dehydrated to achieve an equivalent body weight loss, have a significant 15 mmHg fall in systolic blood pressure. Even when fluid balance is corrected in the Brattleboro rats by the continuous administration of 1-desamino-8-D-arginine vasopressin, a synthetic vasopressin analogue with potent antidiuretic properties but minimal pressor activity, blood pressure still falls when the animals are dehydrated. In contrast, Brattleboro rats infused with exogenous arginine vasopressin to produce a plasma vasopressin level of 18.9 +/- 3.5 pg X ml-1 are able to maintain normal blood pressure during 48 h of dehydration. This level of vasopressin is comparable to the level found endogenously in dehydrated Long-Evans rats and is nonpressor in normal rats. These results suggest that both the antidiuretic and vasoconstrictor properties of vasopressin are important in the cardiovascular response to dehydration.


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