The abnormal renal vasodilator response to D1-like receptor stimulation in conscious SHR can be normalized by AT1 blockade.
2004
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 1 3 1 I-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.
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