The abnormal renal vasodilator response to D1-like receptor stimulation in conscious SHR can be normalized by AT1 blockade
The abnormal renal vasodilator response to D1-like receptor stimulation in conscious SHR can be normalized by AT1 blockade
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DOI：
10.1097/00005344-200411000-00009
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发表时间：
2004-11-01
影响因子：
3
通讯作者：
Navis, G
中科院分区：
文献类型：
--
作者：
de Vries, PAM;de Zeeuw, D;Navis, G
背景资料：我们以前的研究表明，与WKY大鼠相比，清醒SHR对D-1样受体激动剂的肾血管舒张反应减弱。这种受损的多巴胺能反应性在SHR的机制尚不清楚。可能涉及肾素-血管紧张素-醛固酮系统（RAAS）和多巴胺能系统之间的平衡改变。为了确定RAAS和多巴胺能系统在SHR D-1样反应性减弱中的相互作用，我们研究了清醒SHR和WKY大鼠在用AT（1）-受体拮抗剂（AT（1）-A）L158，809预处理7天之前和之后对D-1样受体激动剂非诺多泮的肾血管舒张反应。有效肾血浆流量（ERPF）通过I-131-马尿酸清除率测定。结果：非诺多泮在未经预处理的情况下，使WKY（-7 ± 4%，ns）和SHR（-6 ± 1%，P < 0.05）的MAP降低程度相当。非诺多泮对WKY大鼠ERPF的增加（+26 +/-2%，P <0.0001）显著高于SHR（+2 +/-2%，ns）。AT（1）-A处理后，两株大鼠的MAP均显著降低，ERPF和肾小球滤过率均显著升高.用AT（1）-A预处理显著增强了SHR中非诺多泮诱导的ERPF升高，但在WKY中没有，而不影响两种品系的血压反应。结果，在AT（1）-A预处理期间，非诺多泮引起的ERPF升高在两种品系中相似（SHR +25 +/-2%，P < 0.0001; WKY +33 +/-2%，P < 0.0001）。结论：这些结果表明，RAAS解释了SHR肾血管对D-1样受体激动剂的反应减弱。多巴胺能系统和RAAS之间的失衡可能参与了SHR肾血流动力学调节的异常。
Background: We previously showed that the renal vasodilator response to a D-1-like receptor agonist is blunted in conscious SHR compared with WKY rats. The mechanism of this impaired dopaminergic responsiveness in SHR is unclear. An altered balance between the renin-angiotensin-aldosterone system (RAAS) and the dopaminergic system may be involved. To determine the interaction between the RAAS and the dopaminergic system in the blunted D-1-like responsiveness in SHR, we studied the renal vasodilator response to the D-1-like receptor agonist fenoldopam before and after 7 days of pretreatment with the AT(1)-receptor antagonist (AT(1)-A) L158,809 in conscious SHR and WKY rats.Methods: Effective renal plasma flow (ERPF) was measured by the clearance of I-131-hippuran. Mean arterial pressure (MAP) was measured via an intraarterial catheter.Results: Without pretreatment, MAP was reduced to comparable degrees by fenoldopam in WKY (-7 +/- 4%, ns) and SHR (-6 +/- 1%, P < 0.05). However, ERPF was significantly more increased (P < 0.006) by fenoldopam in WKY (+26 +/- 2%, P < 0.0001) than in SHR (+2 +/- 2%, ns). AT(1)-A treatment reduced MAP and increased ERPF and glomerular filtration rate significantly in both strains. Pretreatment with AT(1)-A significantly potentiated the fenoldopam-induced rise in ERPF in SHR, but not in WKY, without affecting the blood pressure responses in either strain. As a result, during pretreatment with an AT(1)-A, the rise in ERPF by fenoldopam was similar in both strains (SHR +25 +/- 2%, P < 0.0001; WKY +33 +/- 2%, P < 0.0001).Conclusions: These results suggest that the RAAS accounts for the blunted renal vasodilator response to a D-1-like receptor agonist in SHR. A dysbalance between the dopaminergic system and the RAAS may be involved in the abnormal renal hemodynamic regulation in SHR.