Dopamine D ₁ Receptor Augmentation of D ₃ Receptor Action in Rat Aortic or Mesenteric Vascular Smooth Muscles

Abstract

Abstract-Dopamine is an important modulator of blood pressure, in part, by regulating vascular resistance. To test the hypothesis that D 1 and D 3 receptors interact in vascular smooth muscle cells, we studied A10 cells, a rat aortic smooth muscle cell line, and rat mesenteric arteries that express both dopamine receptor subtypes. Both D 1 and D 3 receptors are expressed in vascular smooth muscle cells, and the activation of the D 1 receptor relaxes blood vessels and decreases blood pressure. 5,6 However, the effect of D 3 receptors on resistance vessels is not clear. A low intravenous dose of R(ϩ)-7-hydroxydipropyl-aminotetralin (7-OH-DPAT), a D 2 -like agonist with a 50-fold selectivity for the D 3 over the D 2 receptor, constricts postglomerular arterioles without affecting systemic blood pressure. 4 A higher dose, however, decreases blood pressure. 4 To test the hypothesis that D 1 and D 3 receptors interact in vascular smooth muscle cells, we studied the effect of fenoldopam, a D 1 -like receptor agonist, on D 1 and D 3 receptor expressions in rat thoracic aorta-derived smooth muscle cell line (A10). 7 We also studied the effect of D 1 and D 3 receptor agonists on the wall tension of rat mesenteric arterial rings.

Avaliação Da Função Glomerular De Cães Sadios E Nefropatas Sob Estimulação Dopaminérgica

“…Outra explicação possível seria a diminuição da afinidade dos receptores D1 no leito vascular renal, como ocorre em ratos com hipertensão sistêmica (Ladines, et al, 2001). A estimulação de receptores D3 pode causar constrição da arteríola eferente quando o tônus vascular em repouso está baixo (Zeng, et al, 2004), porém este apresenta-se elevado nos pacientes nefropatas (Hand, et al, 1999), tornando a vasoconstrição induzida por estes receptores pouco provável. Deve-se ressaltar que a pressão arterial sistêmica não apresentou diferença significativa e os valores mantiveram-se dentro do intervalo de referência para a espécie.…”

“…A vasoconstrição da arteríola eferente, que poderia induzir aumento na TFG e U-P/C sem alterar o fluxo sanguíneo renal (Carey, 2001), parece pouco provável. Este fenômeno pode ser induzido pela estimulação de receptores D3, desde que o tônus vascular em repouso esteja baixo (Zeng, et al, 2004), o que não ocorre em pacientes com doença renal (Hand et al, 1999). Além disso, a estimulação de receptores dopaminérgicos D1 diminui a resposta renal à angiotensina II, que é um agente vasoconstritor renal conhecido (Barnett et al, 1986 (Furukawa et al, 2002).…”

Aberrant D 1 and D 3 Dopamine Receptor Transregulation in Hypertension

“…23 In A10 and RPT cells from normotensive rats, D 1 receptor stimulation with a D 1 -like agonist, fenoldopam, increases D 1 receptor protein expression. 23,25 In contrast, in RPT cells from SHRs, fenoldopam has no effect of D 1 receptor expression. 25 The current study extends our previous reports and has several novel observations.…”

“…Figure 2A, the 45-kDa band, representing the co-immunoprecipitated D 3 and D 1 receptors, was increased by a 24-hour treatment of fenoldopam (10 Ϫ7 M) in RPT cells from WKY rats, consistent with our previous report in aortic vascular smooth muscle cells. 23 However, no effect was observed in SHRs (WKY: controlϭ25Ϯ4 DU, fenoldopamϭ40Ϯ3 DU; nϭ7, PϽ0.05; SHRs: controlϭ18Ϯ3 DU, fenoldopamϭ17Ϯ3 DU; nϭ7, PϭNS).…”

“…These effects were specific, because the D 1 -like receptor antagonist, SCH23390, and D 3 receptor antagonist, U99194A, did not have any effect by themselves but blocked the vasorelaxant effects of their respective agonists. 23 There was an interaction between D 1 and D 3 receptors because fenoldopam-induced vasorelaxation was greater in vessels preincubated with PD128907 than in vehicle-treated vessels (Table, Figure 4C). …”