Estrogen or the AT1 antagonist olmesartan reverses the development of profound hypertension in the Congenic mRen2.Lewis rat
Estrogen or the AT1 antagonist olmesartan reverses the development of profound hypertension in the Congenic mRen2.Lewis rat
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DOI：
10.1161/01.hyp.0000085210.66399.a3
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发表时间：
2003-10-01
期刊：
影响因子：
8.3
通讯作者：
Brosnihan, KB
中科院分区：
文献类型：
--
作者：
Chappell, MC;Gallagher, PE;Brosnihan, KB
雌激素对心血管功能调节的影响仍然是一个有争议且复杂的研究领域。我们评估了雌激素缺乏对同源MREN(2).Lewis大鼠的影响，该大鼠是从原始的(MRen2)-27转基因大鼠与Lewis近交系的回交建立的。卵巢切除杂合子MREN(2)。与假手术组相比，Lewis在4~5周的血压在6~11周时逐渐升高。在11周时，卵巢切除的MREN(2)。Lewis(OVX)的平均收缩压为195+/-3.7 mm Hg，而假手术组为141+/-4.0 mm Hg。血浆血管紧张素II、血清血管紧张素转换酶活性、血浆肾素浓度、尿血管紧张素Ⅱ、8-异前列腺素F-2α和内皮素-1排泄量均升高，而肾组织eNOS基因表达水平则受到抑制。雌激素替代治疗可将低于假手术组和去卵巢组的血压降低11周(125+/-2.9毫米汞，n=7，与去卵巢组和假手术组相比，P<；0.01)。此外，AT(1)受体拮抗剂奥美沙坦(CS866；12-16周)基本上使血压正常化至113±5.4 mm Hg(n=6，P<；0.01与OVX和Sham相比)。完全停药7周后，高血压的缓解仍然明显(23周时为124+/-4.1 mm Hg)。总而言之，OVX mRen.2.Lewis表现出血压的快速和持续上升。雌激素或奥美沙坦以类似的程度降低血压。我们认为卵巢对mRen2的血压调节有相当大的影响。可能是通过限制肾素-血管紧张素系统的激活。雌激素对心血管功能调节的影响仍然是一个有争议和复杂的研究领域。我们评估了雌激素缺乏对同源MREN(2).Lewis大鼠的影响，该大鼠是从原始的(MRen2)-27转基因大鼠与Lewis近交系的回交建立的。卵巢切除MREN杂合子(2)。与假手术组相比，Lewis在4-5周导致血压在6-11周进行性升高。在11周，去卵巢MREN(2)。Lewis(OVX)收缩压平均为195+/-3.7min Hg比假手术组141+/-4.0 mm Hg。血浆血管紧张素II、血清血管紧张素转换酶活性、血浆肾素浓度、尿血管紧张素Ⅱ、8-异前列腺素F-2α和内皮素-1排泄量均升高，而肾组织eNOS基因表达水平则受到抑制。雌激素替代治疗可使假手术组和卵巢切除组的血压降低11周(125+/-2.9 mm Hg，n=7，P
The influence of estrogen on the regulation of cardiovascular function remains a controversial and complex area of investigation. We assessed the effects of estrogen depletion in the congenic mRen(2).Lewis rat, established from the back-cross of the original (mRen2)-27 transgenic onto the Lewis inbred strain. Ovariectomy of heterozygous mRen( 2). Lewis at 4 to 5 weeks resulted in a progressive increase in blood pressure compared with the sham surgery congenics at weeks 6 to 11. At 11 weeks, the ovariectomized mRen( 2). Lewis (OVX) systolic blood pressure averaged 195 +/- 3.7 mm Hg versus 141 +/- 4.0 mm Hg for sham. Plasma Angiotensin (Ang) II, serum ACE activity, plasma renin concentration, as well as urinary excretion of Ang II, 8-isoprostane F-2alpha, and endothelin-1 were elevated; however, renal mRNA levels of eNOS were suppressed after ovariectomy. Estrogen replacement reduced blood pressure below both the sham and OVX by 11 weeks (125 +/- 2.9 mm Hg, n = 7, P < 0.01 versus OVX and sham). Moreover, the AT(1) receptor antagonist olmesartan (CS866; week 12 to 16) essentially normalized blood pressure to 113 ± 5.4 mm Hg (n = 6, P < 0.01 versus OVX and sham). The attenuation of the hypertension was still evident 7 weeks after complete withdrawal of treatment (124 +/- 4.1 mm Hg at week 23). In summary, the OVX mRen.2.Lewis exhibited a rapid and sustained increase in blood pressure. Estrogen or olmesartan lowered pressure by a similar extent. We conclude that the ovary exerts considerable influence on the regulation of the blood pressure in the mRen2. Lewis strain, possibly by limiting activation of the renin-angiotensin system.The influence of estrogen on the regulation of cardiovascular function remains a controversial and complex area of investigation. We assessed the effects of estrogen depletion in the congenic mRen(2).Lewis rat, established from the back-cross of the original (mRen2)-27 transgenic onto the Lewis inbred strain. Ovariectomy of heterozygous mRen(2).Lewis at 4 to 5 weeks resulted in a progressive increase in blood pressure compared with the sham surgery congenics at weeks 6 to 11. At 11 weeks, the ovariectomized mRen(2).Lewis (OVX) systolic blood pressure averaged 195 +/- 3.7 min Hg versus 141 +/- 4.0 mm Hg for sham. Plasma Angiotensin (Ang) II, serum ACE activity, plasma renin concentration, as well as urinary excretion of Ang II, 8-isoprostane F-2alpha, and endothelin-1 were elevated; however, renal mRNA levels of eNOS were suppressed after ovariectomy. Estrogen replacement reduced blood pressure below both the sham and OVX by 11 weeks (125 +/- 2.9 mm Hg, n=7, P