scholarly journals Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

2012 ◽  
Vol 13 (3) ◽  
pp. 341-352 ◽  
Author(s):  
Juan Gao ◽  
Jie Chao ◽  
Karma-Jaya K Parbhu ◽  
Li Yu ◽  
Liang Xiao ◽  
...  

In the current experiment, we determined angiotensin type 2 receptor (AT2R) and angiotensin type 1 receptor (AT1R) protein expression by western blot analysis in developing normal mice. The results indicate that: (1) in all detected brain regions and in the spinal cord, adult mice exhibited significantly higher AT2R expression and lower AT1R expression in total protein extracts compared to fetuses and neonates; (2) other major organs, including heart, lung, liver and kidney, exhibited the same expression pattern as the brain and spinal cord; (3) reciprocal changes in AT2R and AT1R expression were found in the total protein extracts from the brainstems of mice from one-day prenatal to six weeks of age, and there was a negative correlation between AT2R and AT1R protein expression; (4) in both membrane and cytosolic fractions from the brainstem, adult mice exhibited higher AT2R and lower AT1R expression than did fetuses and neonates; and (5) in the brainstem, there were no significant differences in AT2R and AT1R messenger RNA (mRNA) levels among fetal, neonatal and adult mice. The above results reconfirmed our previous finding in rats that adult animals have higher AT2R and lower AT1R expression compared to fetuses and neonates. These data imply an involvement of AT1R in fetal development and of AT2R in adult function.

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Katrina M Mirabito Colafella ◽  
Lucinda M Hilliard ◽  
Donna L Ralph ◽  
Jasmine S Manwani ◽  
Tracey Gaspari ◽  
...  

Arterial pressure is age and sex dependent. The angiotensin type 2 receptor (AT 2 R) plays a greater role in the regulation of arterial pressure and renal function in adult females than age-matched males and aging females. In the present study, we investigated the effect of chronic AT 2 R stimulation using the AT 2 R agonist, compound 21 (C21), to attenuate the hypertensive effects of AngII. Mean arterial pressure (MAP) was measured via radiotelemetry in 14 week old male and female mice treated with vehicle, AngII (36 μg/kg/hr), C21 (18 μg/kg/hr), AngII+C21 or AngII+C21 plus PD123319 (AT 2 R antagonist; 125 μg/kg/hr) for 21 days. At the end of the treatment, renal excretory function, angiotensin receptor expression and sodium transporter profiles were assessed. In agreement with previous studies, the pressor response to AngII was greater in male than female mice (35±3 vs 20±4 mmHg respectively, P<0.05). There was no effect of C21 treatment alone on MAP nor did C21 alter the pressor response to AngII in females. However, in males, C21 blunted the pressor response to AngII such that MAP was similar between AngII+C21 males, AngII females and AngII+C21 females (18±2, 20±4 and 17±4 mmHg on day 21, respectively). Co-infusion of PD123319 restored the normal pressor response to AngII in males. Conversely, in females, treatment with AngII+PD123319 or AngII+C21+PD123319 enhanced the pressor response to AngII by ~20 mmHg, to a level seen in AngII males. The renal AT 2 R/AT 1 R ratio was greater in female than male mice and was not affected by treatment. Vehicle treated females had lower proximal versus distal Na+ transporter abundance than males. AngII-treatment increased NCC in both sexes, while proximal and loop transporters (NHE, NHE3-P, NaPi2 and NKCC2) decreased in males only. Treatment with C21 alone did not significantly affect sodium transporters. In males, AngII+C21treatment increased distal transporters and this effect was reversed by PD123319. Conversely, in females, C21 blunted the AngII effect on sodium transporters (claudin-2, NKCC-P, NCC-P and ENaC). Our novel data demonstrate that chronic AT 2 R stimulation attenuates AngII-induced hypertension in adult males, but not females. Thus, AT 2 R agonists may be a novel antihypertensive therapy for males and ageing females.


2007 ◽  
Vol 77 (3) ◽  
pp. 560-569 ◽  
Author(s):  
Qiuhong Zhang ◽  
Fengtian He ◽  
Ramalinga Kuruba ◽  
Xiang Gao ◽  
Annette Wilson ◽  
...  

Hypertension ◽  
2019 ◽  
Vol 74 (4) ◽  
pp. 967-974 ◽  
Author(s):  
Jay S. Mishra ◽  
Gigi M. te Riele ◽  
Qian-Rong Qi ◽  
Thomas J. Lechuga ◽  
Kathirvel Gopalakrishnan ◽  
...  

2014 ◽  
Vol 307 (8) ◽  
pp. F901-F907 ◽  
Author(s):  
Katrina M. Mirabito ◽  
Lucinda M. Hilliard ◽  
Michelle M. Kett ◽  
Russell D. Brown ◽  
Sean C. Booth ◽  
...  

Sex hormones regulate the renin-angiotensin system. For example, estrogen enhances expression of the angiotensin type 2 receptor. We hypothesized that activation of the angiotensin type 2 receptor shifts the chronic pressure-natriuresis relationship leftward in females compared with males and that this effect is lost with age. Mean arterial pressure was measured by radiotelemetry in adult (4 mo old) and aged (14 mo old) wild-type and angiotensin type 2 receptor knockout male and female mice. Chronic pressure-natriuresis curves were constructed while mice were maintained on a normal-salt (0.26%) diet and following 6 days of high salt (5.0%) diet. Mean arterial pressure was lower in adult wild-type females than males (88 ± 1 and 97 ± 1 mmHg, respectively), a difference that was maintained with age, but was absent in adult knockout mice. In wild-type females, the chronic pressure-natriuresis relationship was shifted leftward compared with knockout females, an effect that was lost with age. In males, the chronic pressure-natriuresis relationship was not influenced by angiotensin type 2 receptor deficiency. Compared with age-matched females, the chronic pressure-natriuresis relationships in male mice were shifted rightward. Renal expression of the angiotensin type 2 receptor was fourfold greater in adult wild-type females than males. With age, the angiotensin type 2 receptor-to-angiotensin type 1 receptor balance was reduced in females. Conversely, in males, angiotensin receptor expression did not vary significantly with age. In conclusion, the angiotensin type 2 receptor modulates the chronic pressure-natriuresis relationship in an age- and sex-dependent manner.


2016 ◽  
Vol 130 (10) ◽  
pp. 761-771 ◽  
Author(s):  
Katrina M. Mirabito Colafella ◽  
Lucinda M. Hilliard ◽  
Kate M. Denton

The renin–angiotensin system (RAS) plays a commanding role in the regulation of extracellular fluid homoeostasis. Tigerstadt and Bergman first identified the RAS more than two centuries ago. By the 1980s a voyage of research and discovery into the mechanisms and actions of this system led to the development of drugs that block the RAS, which have become the mainstay for the treatment of cardiovascular and renal disease. In the last 25 years new components of the RAS have come to light, including the angiotensin type 2 receptor (AT2R) and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1–7) [Ang(1–7)]/Mas receptor (MasR) axis. These have been shown to counter the classical actions of angiotensin II (AngII) at the predominant angiotensin type 1 receptor (AT1R). Our studies, and those of others, have demonstrated that targeting these depressor RAS pathways may be therapeutically beneficial. It is apparent that the evolution of both the pressor and depressor RAS pathways is distinct throughout life and that the depressor/pressor balance of the RAS vary between the sexes. These temporal patterns of expression suggest that therapies targeting the RAS could be optimized for discrete epochs in life.


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