cardiovascular system
• the diameter of the right common carotid artery is reduced and its walls are thicker
|
• homozygotes display a higher mean arterial pressure than wild-type controls
• however, no significant difference in heart rate is observed
|
• unlike in wild-type controls, chronic ligation of the left external carotid artery fails to result in a reduction in the lumen diameter of the left common carotid artery and medial wall thickness is increased, indicating a defect in flow-dependent vascular remodeling
|
• in response to blood flow stimulation, isolated mutant endothelial cells fail to exhibit a shear stress-dependent increase in Ca2+ influx and subsequent production of the potent vasodilator nitric oxide (NO)
• adenovirus vector-mediated gene transfer rescues the impaired flow-induced influx of Ca2+ and production of NO in cultured endothelial cells
|
• ATP-, but not acetylcholine-induced, vasodilation is significantly suppressed in preconstricted mutant cremaster muscle arterioles relative to wild-type arterioles
• following occlusion of one arteriole branch with a glass micropipette to increase blood flow through the other branch, flow-induced vasodilation is significantly reduced in mutant cremaster muscle arterioles relative to wild-type arterioles
• both ATP- and flow-induced (shear stress, 20 dynes/cm2), but not acetylcholine-induced, vasodilation is significantly reduced in mutant mesenteric arteries relative to wild-type arteries
• addition of EGTA or L-NAME significantly reduces flow-induced vasodilation in both genotypes, indicating that Ca2+ influx and NO mediate the vasodilatory response
|
muscle
• ATP-, but not acetylcholine-induced, vasodilation is significantly suppressed in preconstricted mutant cremaster muscle arterioles relative to wild-type arterioles
• following occlusion of one arteriole branch with a glass micropipette to increase blood flow through the other branch, flow-induced vasodilation is significantly reduced in mutant cremaster muscle arterioles relative to wild-type arterioles
• both ATP- and flow-induced (shear stress, 20 dynes/cm2), but not acetylcholine-induced, vasodilation is significantly reduced in mutant mesenteric arteries relative to wild-type arteries
• addition of EGTA or L-NAME significantly reduces flow-induced vasodilation in both genotypes, indicating that Ca2+ influx and NO mediate the vasodilatory response
|
homeostasis/metabolism
• mutant endothelial cells fail to exhibit flow-induced production of NO
• homozygotes excrete reduced amounts of NO products in urine
|
• homozygotes show a significant reduction in the daily amount of nitrite (and nitrate) excreted in urine relative to wild-type controls
|
renal/urinary system
• homozygotes show a significant reduction in the daily amount of nitrite (and nitrate) excreted in urine relative to wild-type controls
|