cardiovascular system
• older mice develop cardiac perivascular fibrosis
|
hypertension
(
J:227997
)
• systolic and diastolic blood pressure are increased in young (90 day) male and female mice
• hydrochlorothiazide reduces, but does not normalize, blood pressure
• mice treated with hydralazine, a vascular smooth muscle cell relaxant, show a drop in blood pressure as is seen with controls, however, endothelial dysfunction is not normalized and glomerular lesions are only partially reduced
|
• a high-salt diet increases blood pressure in 8 month old mice, while a low-salt diet decreases blood pressure without normalizing it
• regular salt diet for 4 weeks after the end of high- or low-salt diet brings blood pressure back to its initial level, indicating that mice develop salt sensitivity with age
|
• in young mice
|
• in young mice
|
• vasodilatory response to acetylcholine is decreased in mesenteric arteries
• however, vasoconstrictor response of mesenteric arteries to phenylephrine is similar to controls and vasodilatory response to ethylamine NONOate, an NO donor, is similar to controls
|
immune system
• leukocyte infiltration is increased 2-fold in renal cortex, all around the tubules and the glomeruli
• inflammatory and kidney injury markers and inflammatory cell infiltrates are increased in older animals
• treatment with hydralazine abrogates renal inflammation
|
muscle
• vasodilatory response to acetylcholine is decreased in mesenteric arteries
• however, vasoconstrictor response of mesenteric arteries to phenylephrine is similar to controls and vasodilatory response to ethylamine NONOate, an NO donor, is similar to controls
|
renal/urinary system
• proteinuria in older mice
• however, urinary excretion of sodium, potassium, and chloride and electrolytes, and plasma electrolyte concentrations are unchanged
|
• leukocyte infiltration is increased 2-fold in renal cortex, all around the tubules and the glomeruli
• inflammatory and kidney injury markers and inflammatory cell infiltrates are increased in older animals
• treatment with hydralazine abrogates renal inflammation
|
• older mice develop features of hypertensive nephropathy
|
• glomerular cellularity is increased
|
• older mice exhibit segmental glomerulosclerosis with mesangial cell proliferation, glomerular basement membrane thickening, and accumulation of extracellular matrix
|
• in older mice
|
homeostasis/metabolism
• proteinuria in older mice
• however, urinary excretion of sodium, potassium, and chloride and electrolytes, and plasma electrolyte concentrations are unchanged
|
• plasma renin activity is slightly, but significantly, decreased
• however, urinary aldosterone concentrations are normal
|
behavior/neurological
N |
• no differences in food and water intake
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
essential hypertension | DOID:10825 |
OMIM:145500 OMIM:603918 OMIM:604329 OMIM:607329 OMIM:608742 OMIM:610261 OMIM:610262 OMIM:610948 OMIM:611014 |
J:227997 |