Stimulation of angiotensin II receptor 2 preserves cognitive function and is associated with an enhanced cerebral vascular density after stroke

2021 ◽  
pp. 106904
Author(s):  
Wael Eldahshan ◽  
Mohammed A. Sayed ◽  
Mohamed E. Awad ◽  
Heba A. Ahmed ◽  
Ellen Gillis ◽  
...  
1995 ◽  
Vol 269 (1) ◽  
pp. F86-F92 ◽  
Author(s):  
G. T. Nagami

Angiotensin II is an important regulator of acid-base and ammonia metabolism in the proximal tubule. Because angiotensin II receptors exist on the apical membrane and because luminal fluid angiotensin II concentrations may be substantial, the effects of luminal angiotensin II on ammonia production rates and net luminal total ammonia (tNH3) secretion rates were examined in dissected mouse S2 proximal tubule segments. Ammonia production rates reflected the total release of ammonia via the basolateral and luminal aspects of the tubule, whereas net luminal secretion rates reflected the rates at which ammonia left the tubule via the luminal fluid leaving the distal end of the perfused segment. The results demonstrated that 1) luminal angiotensin II affected tNH3 production in a concentration-dependent fashion, 2) luminal angiotensin II at concentrations that stimulated tNH3 production could counteract the effect of inhibitory basolateral concentrations of angiotensin II, 3) the stimulation of tNH3 production and the rise in intracellular calcium concentration induced by 10(-10) M luminal angiotensin II were blocked by the addition of an angiotensin II receptor inhibitor, saralasin, or the calcium channel blocker nifedipine to the luminal perfusion solution, and 4) in contrast to basolateral angiotensin II, which inhibited net luminal tNH3 secretion, luminal angiotensin II stimulated amiloride-sensitive net luminal tNH3 secretion in parallel with stimulation of luminal fluid acidification. Thus luminal angiotensin II at physiological and superphysiological concentrations has important effects on ammonia production and transport in the proximal tubule that in some ways differ from the effects of basolateral angiotensin II.


2011 ◽  
Vol 32 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Fei Jing ◽  
Masaki Mogi ◽  
Akiko Sakata ◽  
Jun Iwanami ◽  
Kana Tsukuda ◽  
...  

We examined the possibility that direct stimulation of the angiotensin II type 2 (AT2) receptor by a newly generated direct AT2 receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT2 receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B2 receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT2 receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-β (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT2 receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.


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