In vitro: Most of the known actions of Angiotensin II (Ang II) are mediated by AT1 receptors, the AT2 receptor contributes to the regulation of blood pressure and renal function. Angiotensin II raises blood pressure (BP) by a number of actions, the most important ones being vasoconstriction, sympathetic nervous stimulation, increased aldosterone biosynthesis and renal actions. Other Angiotensin II actions include induction of growth, cell migration, and mitosis of vascular smooth muscle cells, increased synthesis of collagen type I and III in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis. These actions are mediated by type 1 Ang II receptors (AT1). At the cellular level, responsiveness to Angiotensin II is conferred by the expression of the two classes of angiotensin receptors (AT1 and AT2). The effects of Angiotensin II to increase blood pressure are mediated by AT1 receptors.
In vivo: To distinguish the AT1 receptor population that is critical for the pathogenesis of hypertension, osmotic minipumps are implanted s.c. into each animal to infuse Angiotensin II (1,000 ng/kg/min) continuously for 4 weeks. Angiotensin II causes hypertension by activating AT1 receptors in the kidney promoting sodium reabsorption.
|Animal models||(129×C57BL/6) F1 mice lacking AT1A receptors for Angiotensin II|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||50 mg/mL in water|
Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney.
Crowley SD, et al. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17985-90. PMID: 17090678.
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