An activated renin-angiotensin system maintains normal blood pressure in aryl hydrocarbon receptor heterozygous mice but not in null mice.
An activated renin-angiotensin system maintains normal blood pressure in aryl hydrocarbon receptor heterozygous mice but not in null mice.
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DOI：
10.1016/j.bcp.2010.03.023
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发表时间：
2010-07-15
影响因子：
5.8
通讯作者：
Walker, Mary K.
中科院分区：
文献类型：
--
作者：
Zhang, Nan;Agbor, Larry N.;Scott, Jason A.;Zalobowski, Tyler;Elased, Khalid M.;Trujillo, Alicia;Duke, Melissa Skelton;Wolf, Valerie;Walsh, Mary T.;Born, Jerry L.;Felton, Linda A.;Wang, Jian;Wang, Wei;Kanagy, Nancy L.;Walker, Mary K.
据推测，芳香烃受体缺失（ahr−/−）小鼠的胎儿血管异常可能会改变成年期的心血管稳态。我们检验了这样一个假设，即与ahr−/−小鼠相比，成年杂合子小鼠（ahr+/−）的血压调节是正常的，因为在杂合子动物中没有血管异常的报道。在用自主神经系统抑制剂、一氧化氮合酶（NOS）、血管紧张素转换酶（ACE）或内皮素-1A受体（ETA）治疗之前和治疗期间，使用无线电遥测术测量平均动脉血压（MAP）。此外，测定了肾素-血管紧张素系统（RAS）激活指数。与野生型（AHR+/+）同窝出生的小鼠相比，AHR+/-和AHR-/-小鼠分别血压正常和水肿。所有基因型对自主神经系统抑制的反应均正常。ahr+/-小鼠对NOS抑制反应正常，而ahr-/-小鼠的反应明显减弱。相比之下，ahr+/-小鼠对ACE抑制、ETA拮抗剂或两者的反应明显更强，而ahr-/-小鼠对ACE抑制的反应明显更弱，对ETA拮抗剂的反应更强。ahr+/−小鼠还表现出血浆肾素和ACE活性、血浆钠和尿渗透压的显著增加，表明RAS激活。因此，ahr+/−小鼠的正常血压似乎是通过RAS和ET-1信号的增加来维持的，而ahr−/−小鼠的低血压可能是由于RAS信号的减少。总之，尽管ahr+/-小鼠没有明显的胎儿血管异常，但单个ahr等位基因的丢失对血压调节有显著影响。
It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr−/−) mice may alter cardiovascular homeostasis in adulthood. We tested the hypothesis that blood pressure regulation in adult heterozygous mice (ahr+/−) would be normal, compared to ahr−/− mice, since no vascular abnormalities have been reported in the heterozygote animals. Mean arterial blood pressure (MAP) was measured using radiotelemetry prior to and during treatment with inhibitors of the autonomic nervous system, nitric oxide synthase (NOS), angiotensin converting enzyme (ACE), or endothelin-1 A receptor (ETA). Also, indices of renin-angiotensin system (RAS) activation were measured. ahr+/− and ahr−/− mice were normotensive and hypotensive, respectively, compared to wild-type (ahr+/+) littermates. Responses of all genotypes to autonomic nervous system inhibition were normal. ahr+/− mice responded normally to NOS inhibition, while the responses of ahr−/− mice were significantly blunted. In contrast, ahr+/− mice were significantly more responsive to inhibition of ACE, an ETA antagonist, or both, while ahr−/− mice were significantly less response to ACE inhibition and more response to an ETA antagonist. ahr+/− mice also exhibited significant increases in plasma renin and ACE activity, plasma sodium, and urine osmolality, indicative of RAS activation. Thus, normotension in ahr+/− mice appears to be maintained by increased RAS and ET-1 signaling, while hypotension in ahr−/− mice may result from decreased RAS signaling. In conclusion, despite the lack of overt fetal vascular abnormalities in ahr+/− mice, the loss of a single ahr allele has a significant effect on blood pressure regulation.
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影响因子：
8.3
作者：
Lund, Amie K.;Agbor, Larry N.;Walker, Mary K.
通讯作者：
Walker, Mary K.
影响因子：
10.8
作者：
Han, Zhiyi;Miwa, Yoshikazu;Sasaguri, Toshiyuki
通讯作者：
Sasaguri, Toshiyuki
DOI：
10.1073/pnas.190256997
发表时间：
2000-09-12
影响因子：
11.1
作者：
Lahvis, GP;Lindell, SL;Bradfield, CA
通讯作者：
Bradfield, CA
DOI：
10.1152/ajpregu.2000.279.5.r1701
发表时间：
2000-11-01
影响因子：
2.8
作者：
Reinhart, GA;Preusser, LC;Cox, BF
通讯作者：
Cox, BF
DOI：
10.1080/10623320490432434
发表时间：
2004-01-01
影响因子：
--
作者：
Eskin, SG;Turner, NA;McIntire, LV
通讯作者：
McIntire, LV