Ll. Tang et al., Biphasic actions of prostaglandin E-2 on the renal afferent arteriole - Role of EP3 and EP4 receptors, CIRCUL RES, 86(6), 2000, pp. 663-670
Prostaglandin (PG) E-2 is an important modulator of the actions of angoiote
nsin (Ang) II, In the present study, we investigated the renal microvascula
r actions of PGE(2) and the EP receptor subtypes involved. Ibuprofen potent
iated Ang II-induced vasoconstriction in in vitro perfused normal rat kidne
ys and augmented afferent arteriolar, but not efferent arteriolar, response
s in the hydronephrotic rat kidney model. This preglomerular effect of endo
genous prostanoids was mimicked by exogenous PGE(2), which reversed Ang II-
induced afferent arteriolar vasoconstriction at concentrations of 0.1 to 10
nmol/L without affecting the efferent arteriole. The PGE(2)-induced vasodi
lation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and wa
s mimicked by 11-deoxy-PGE(1) (0.01 to 1 nmol/L), Butaprost, which acts pre
ferentially at EP2 receptors, was relatively ineffective. Whereas 0.1 to 10
nmol/L PGE(2) elicited vasodilation, higher concentrations (1 to 10 mu mol
/L) restored Ang II-induced afferent arteriolar vasoconstriction. This resp
onse was blocked by pertussis toxin (200 mu g/mL) and was mimicked by the E
P1/EP3 agonist sulprostone (1 to 300 nmol/L). Reverse transcription-polymer
ase chain reaction of individually isolated afferent arterioles revealed th
e presence of message for EP4 and all 3 EP3 splice variants (alpha, beta, a
nd gamma) but not EP1 or EP2. Our findings thus indicate that PGE(2) elicit
s both vasodilatory and vasoconstrictor actions on the afferent arteriole,
The vasodilation is mediated by EP4 receptors coupled to cAMP, presumably v
ia G(alpha s). The vasoconstriction is mediated by an EP3 receptor coupled
to G(alpha 1) and appears to reflect a functional antagonism of the EP4-ind
uced vasodilatio.