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- W2716388104 abstract "Hypertension in many animal models is sensitive to inhibition of the brain renin-angiotensin system (RAS). We examined mice with transgenic hyperactivity of the brain RAS (sRA mice) to determine whether this manipulation is sufficient to cause hypertension, and to identify the causative mechanism. sRA mice exhibit brain-specific increases in angiotensin (ANG) peptide production through neuron-specific expression of human renin (synapsin promoter) and expression of human angiotensinogen through its own promoter. We determined both through tail-cuff and radiotelemetric methods that sRA mice are hypertensive (SBP; control 112±2 vs sRA 127±5 mmHg, P=0.02). Despite normal plasma osmolality and moderate hyponatremia, sRA mice exhibit double the number of vasopressin-expressing neurons in the supraoptic nucleus (P=0.002), as detected by immunohistochemistry. Plasma levels of the vasopressin pro-segment, copeptin, were reduced in sRA mice (140±19 vs 68±21 pg/mL, P=0.02), which correlated with severe polyuria (1.8±0.3 vs 12.3±1.6 mL/day, P<0.001). Indeed, total daily copeptin loss in the urine was significantly increased almost twenty-fold in sRA mice (7.9±4.3 vs 154.4±62.4 pg/day, P=0.03), highlighting an increase in vasopressin secretion per unit time. The baseline hypertension of sRA mice was completely reversed by chronic infusion of the dual V 1A / V 2 receptor antagonist, conivaptan (22 ng/hr, 10 days, s.c.; 113±5 mmHg, P=0.02). Preliminary experiments demonstrate that infusion of the selective V 2 receptor antagonist, tolvaptan (22 ng/hr, 10 days, s.c.), has similar effects. Further, while abdominal aorta and mesenteric arteries demonstrate selective desensitization to vasopressin and down-regulation of the V 1A receptor (38% of control, P<0.05), renal V 2 receptor expression remained normal in sRA mice. Together, these data demonstrate major roles for vasopressin and its V 2 receptor in the hypertension caused by elevated brain RAS activity." @default.
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- W2716388104 date "2012-09-01" @default.
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- W2716388104 title "Abstract 126: Transgenic Hyperactivity of the Brain Renin-Angiotensin System Causes Vasopressin-Dependent Hypertension" @default.
- W2716388104 doi "https://doi.org/10.1161/hyp.60.suppl_1.a126" @default.
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