Analysis Tools
cardiovascular system
| N |
• homozygotes show no differences in body weight or hematocrit relative to wild-type mice under both normoxic and chronically hypoxic conditions
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• under both normoxic and hypoxic conditions, homozygotes display a higher % of muscularized peripheral pulmonary vessels relative to heterozygous or wild-type mice
• under normoxic conditions, homozygotes exhibit a higher % of partially muscularized peripheral pulmonary vessels
• after 3 wks of hypobaric hypoxia, homozygotes exhibit a higher % of fully muscularized peripheral pulmonary vessels
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• on intermediate salt diets (2% NaCl), homozygotes exhibit cardiac enlargement relative to wild-type
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• under normoxic and chronically hypoxic conditions, homozygotes display a higher left ventricle plus septum weight-to-body weight (LV+S/BW) ratio than heterozygous and wild-type mice
• LV+S/BW is 49% and 38% greater in normoxic and chronically hypoxic conditions, respectively, relative to wild-type controls
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• under normoxic and chronically hypoxic conditions, homozygotes display a higher right ventricle weight-to-body weight (RV/BW) ratio than heterozygous and wild-type mice
(J:54986)
• RV/BW is 60% and 53% greater in normoxic and chronically hypoxic conditions, respectively, relative to wild-type controls
(J:54986)
• the RV/LV+S ratio is higher in homozygous mutants than that in heterozygous or wild-type mice under hypoxic but not under normoxic conditions
(J:54986)
• after a 5-wk hypoxic exposure (10% O2), hypoxia-induced increases in RV mass are significantly higher in homozygous than in wild-type (384% vs. 265%, respectively)
(J:64898)
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• on intermediate salt diets (2% NaCl), homozygotes exhibit a greater ratio of heart weight to body weight than both heterozygous and wild-type
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• autonomic ganglion blockade induces comparable per cent reductions in CO, HR, and stroke volume in both genotypes; however, in mutants, the concomitant decrease in ABP (%) is significantly higher than in wild-type mice and is accompanied by a significant reduction in total peripheral resistance
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• homozygotes display a tendency towards reduced cardiac output (CO) values, as a result of reduced basal heart rate (HR); however, the differences in basal CO and HR do not reach statistical significance
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• chronically hypertensive homozygotes exhibit elevated baseline total peripheral resistance relative to normotensive wild-type mice; no differences in stroke volume are observed
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• under normoxic conditions, homozygotes exhibit higher right ventricular peak pressure (RVPP) than wild-type mice
(J:54986)
• after 3 weeks of hypoxia, homozygotes show a higher RVPP than heterozygous or wild-type mice
(J:54986)
• after a 5-wk hypoxic exposure (10% O2), hypoxia-induced increases in right ventricular (RV) pressure are significantly higher in homozygous than in wild-type mice (10417% vs. 4510%, respectively)
(J:64898)
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• when fed on a HS-diet (8% NaCl) for 4 weeks, homozygotes exhibit significantly increased basal heart rates (504 20 beats/min) relative to wild-type (42525 beats/min)
• chronic treatment with the AT1 antagonist losartan has no effect on HR in wild-type mice, but reduces HR to wild-type levels in salt-fed mutant mice
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• homozygotes develop severe hypoxic pulmonary hypertension, as shown by significant differences in RVPP, RV/BW, RV/LV+S, or % of muscularized pulmonary vessels between hypoxia-adapted homozygotes and wild-type mice
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• intracerebroventricular ANP or losartan results in significant (and rapid) hypotension only in homozygous mutant mice
• notably, mutant and wild-type mice show comparable reductions in mean ABP after intravenous injection of vasopressin V1-receptor antagonist, suggesting that increased central AT1-receptor activation, but not systemic vasopressin, sustains chronic hypertension in mutant mice
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hypertension
(
J:76312
)
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• homozygotes exhibit significant increases in blood pressures (8 to 23 mm Hg) when they are fed standard (0.5% NaCl) and intermediate (2% NaCl) salt diets for 2-3 weeks
• the heart rates of homozygotes are comparable to those of wild-type and heterozygous littermates
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• when fed on a HS-diet (8% NaCl) for 4 weeks, homozygotes exhibit significantly increased basal arterial blood pressures (1395 mm Hg) relative to wild-type mice (821 mm Hg)
(J:57623)
• chronic treatment with the AT1 antagonist losartan has no effect on ABP in wild-type mice, but reduces ABP to wild-type levels in salt-fed mutant mice
(J:57623)
• regardless of the state of alertness (i.e. conscious vs. anesthetized), homozygotes develop salt-sensitive hypertension (1353 mm Hg) after prolonged maintenance (>1 wk) on a high-salt (HS; 8% NaCl) diet compared with both homozygotes (1152 mm Hg) and wild-type (1105 mm Hg) mice maintained on a low-salt (LS; 0.008% NaCl) diet
(J:95900)
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• homozygotes display elevated baseline arterial blood pressure (1324 mm Hg) relative to wild-type mice (952 mm Hg)
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hematopoietic system
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• after 2 wk on a high-salt diet, homozygotes exhibit significantly reduced hematocrits relative to wild-type mice, suggesting relative salt-retention during chronic high-salt maintainance
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homeostasis/metabolism
| N |
• homozygotes fed on a HS-diet (8% NaCl) for 4 weeks, display a comparable cumulative dietary intake of food and water and urinary excretion of fluid and electrolytes relative to wild-type; chronic treatment with losartan has no effect on these parameters
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• when fed on a HS-diet (8% NaCl) for 4 weeks, homozygotes exhibit a 10-fold increase in baseline total plasma catecholamine levels (norepinephrine plus epinephrine) relative to wild-type mice, indicating an abnormally elevated sympathetic tone
• chronic treatment with the AT1 antagonist losartan reduces plasma catecholamine to approximately wild-type levels in salt-fed mutant mice
• notably, plasma aldosterone does not differ significantly between genotypes and is not altered by losartan
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• after 2 wks on 8% NaCl, homozygotes show increased sodium reabsorption relative to wild-type mice
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• in homozygotes maintained on a high-salt (HS; 8% NaCl) diet, the salt-sensitive hypertensive response is time-dependent (>1 wk latency), and is associated with failure to downregulate plasma renin activity (PRA)
• in contrast, wild-type mice respond to HS diet with an appropriate reduction in PRA relative to wild-type mice maintained on low-salt diet (LS; 0.008% NaCl), and remain normotensive for the duration of the dietary regimen
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muscle
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• under both normoxic and hypoxic conditions, homozygotes display a higher % of muscularized peripheral pulmonary vessels relative to heterozygous or wild-type mice
• under normoxic conditions, homozygotes exhibit a higher % of partially muscularized peripheral pulmonary vessels
• after 3 wks of hypobaric hypoxia, homozygotes exhibit a higher % of fully muscularized peripheral pulmonary vessels
|
|
• under normoxic and chronically hypoxic conditions, homozygotes display a higher left ventricle plus septum weight-to-body weight (LV+S/BW) ratio than heterozygous and wild-type mice
• LV+S/BW is 49% and 38% greater in normoxic and chronically hypoxic conditions, respectively, relative to wild-type controls
|
|
• under normoxic and chronically hypoxic conditions, homozygotes display a higher right ventricle weight-to-body weight (RV/BW) ratio than heterozygous and wild-type mice
(J:54986)
• RV/BW is 60% and 53% greater in normoxic and chronically hypoxic conditions, respectively, relative to wild-type controls
(J:54986)
• the RV/LV+S ratio is higher in homozygous mutants than that in heterozygous or wild-type mice under hypoxic but not under normoxic conditions
(J:54986)
• after a 5-wk hypoxic exposure (10% O2), hypoxia-induced increases in RV mass are significantly higher in homozygous than in wild-type (384% vs. 265%, respectively)
(J:64898)
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renal/urinary system
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• after 2 wks on 8% NaCl, homozygotes show increased sodium reabsorption relative to wild-type mice
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growth/size/body
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• on intermediate salt diets (2% NaCl), homozygotes exhibit cardiac enlargement relative to wild-type
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• under normoxic and chronically hypoxic conditions, homozygotes display a higher left ventricle plus septum weight-to-body weight (LV+S/BW) ratio than heterozygous and wild-type mice
• LV+S/BW is 49% and 38% greater in normoxic and chronically hypoxic conditions, respectively, relative to wild-type controls
|
|
• under normoxic and chronically hypoxic conditions, homozygotes display a higher right ventricle weight-to-body weight (RV/BW) ratio than heterozygous and wild-type mice
(J:54986)
• RV/BW is 60% and 53% greater in normoxic and chronically hypoxic conditions, respectively, relative to wild-type controls
(J:54986)
• the RV/LV+S ratio is higher in homozygous mutants than that in heterozygous or wild-type mice under hypoxic but not under normoxic conditions
(J:54986)
• after a 5-wk hypoxic exposure (10% O2), hypoxia-induced increases in RV mass are significantly higher in homozygous than in wild-type (384% vs. 265%, respectively)
(J:64898)
|
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• on intermediate salt diets (2% NaCl), homozygotes exhibit a greater ratio of heart weight to body weight than both heterozygous and wild-type
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hypertension | DOID:10763 | J:76312 | ||
