Angiotensin-II type 1 receptor-mediated hypertension in D4 dopamine receptor-deficient mice
Angiotensin-II type 1 receptor-mediated hypertension in D4 dopamine receptor-deficient mice
复制标题
DOI：
10.1161/01.hyp.0000198427.96225.36
复制
发表时间：
2006-02-01
期刊：
影响因子：
8.3
通讯作者：
Jose, PA
中科院分区：
文献类型：
--
作者：
Bek, MJ;Wang, XY;Jose, PA
多巴胺受体在全身血压调节中很重要。D-4受体在肾脏和大脑中表达，但它们在心血管调节中的作用尚不清楚。在戊巴比妥麻醉小鼠中，与D-4野生型（D-4(+/+)）小鼠相比，第6代D-4受体缺乏（D-4(-/-)）小鼠和第10代D-4（-/-）小鼠的收缩压和舒张压升高。通过慢性动脉（股）导管或遥测（颈动脉）测量的有意识血压在D-4（-/-）小鼠中也高于D4窝鼠。2个小鼠品系的肾素和血浆肾素浓度相似。相对于D-4（+/+）小鼠（肾：100 +/- 12%，n = 5；脑：100 +/- 32%，n = 5）， D-4（-/-）小鼠肾（330 +/- 53%,n = 5）和脑（272 +/- 69%,n = 5）匀浆中血管紧张素II型1受体蛋白表达增加。D-4（-/-）小鼠肾膜受体表达量（289 +/- 28%,n = 8）高于D-4(+/)+小鼠（100 +/- 14%,n = 10）。相比之下，2株在心脏中的表达相似。静脉注射血管紧张素II型1受体拮抗剂氯沙坦最初降低D-4（-/-）和D-4（+/+）幼崽平均动脉压的程度相似。然而，在D-4（+/+）小鼠中，氯沙坦的降压作用在10分钟后消失，而在D-4（-/-）小鼠中，这种作用持续了45分钟。我们得出结论，D-4受体的缺失会增加血压，可能是通过增加血管紧张素II型1受体的表达。
Dopamine receptors are important in systemic blood pressure regulation. D-4 receptors are expressed in the kidney and brain, but their role in cardiovascular regulation is unknown. In pentobarbital-anesthetized mice, systolic and diastolic blood pressures were elevated in sixth-generation D-4 receptor - deficient (D-4(-/-)) mice and in tenth-generation D-4(-/-) mice compared with D-4 wild-type (D-4(+/+)) littermates. The conscious blood pressures measured via a chronic arterial ( femoral) catheter or telemetry ( carotid) were also higher in D-4(-/-) mice than in D4 littermates. Basal renal and plasma renin concentrations were similar in the 2 mouse strains. The protein expression of angiotensin II type 1 receptor was increased in homogenates of kidney ( 330 +/- 53%, n = 5) and brain ( 272 +/- 69%, n = 5) of D-4(-/-) mice relative to D-4(+/+) mice ( kidney: 100 +/- 12%, n = 5; brain: 100 +/- 32%, n = 5). The expression of the receptor in renal membrane was also increased in D-4(-/-) mice (289 +/- 28%, n = 8) relative to D-4(+/)+ mice ( 100 +/- 14%, n = 10). In contrast, the expression in the heart was similar in the 2 strains. Bolus intravenous injection of angiotensin II type 1 receptor antagonist losartan initially decreased mean arterial pressures to a similar degree in D-4(-/-) and D-4(+/+) littermates. However, the hypotensive effect of losartan dissipated after 10 minutes in D-4(+/+) mice, whereas the effect persisted for > 45 minutes in D-4(-/-) mice. We conclude that the absence of the D-4 receptor increases blood pressure, possibly via increased angiotensin II type 1 receptor expression.