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(Circulation Research. 2000;86:663.)
© 2000 American Heart Association, Inc.

Integrative Physiology

Biphasic Actions of Prostaglandin E₂ on the Renal Afferent Arteriole

Role of EP₃ and EP₄ Receptors

Lilong Tang, Kathy Loutzenhiser, Rodger Loutzenhiser

From the Smooth Muscle Research Group, Department of Pharmacology and Therapeutics, The University of Calgary, Calgary, Alberta, Canada.

Correspondence to Rodger D. Loutzenhiser, PhD, Department of Pharmacology and Therapeutics, The University of Calgary, Health Sciences Centre, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada. E-mail rloutzen{at}ucalgary.ca

Abstract—Prostaglandin (PG) E₂ is an important modulator of the actions of angiotensin (Ang) II. In the present study, we investigated the renal microvascular actions of PGE₂ and the EP receptor subtypes involved. Ibuprofen potentiated Ang II–induced vasoconstriction in in vitro perfused normal rat kidneys and augmented afferent arteriolar, but not efferent arteriolar, responses in the hydronephrotic rat kidney model. This preglomerular effect of endogenous prostanoids was mimicked by exogenous PGE₂, which reversed Ang II–induced afferent arteriolar vasoconstriction at concentrations of 0.1 to 10 nmol/L without affecting the efferent arteriole. The PGE₂-induced vasodilation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and was mimicked by 11-deoxy-PGE₁ (0.01 to 1 nmol/L). Butaprost, which acts preferentially at EP₂ receptors, was relatively ineffective. Whereas 0.1 to 10 nmol/L PGE₂ elicited vasodilation, higher concentrations (1 to 10 µmol/L) restored Ang II–induced afferent arteriolar vasoconstriction. This response was blocked by pertussis toxin (200 µg/mL) and was mimicked by the EP₁/EP₃ agonist sulprostone (1 to 300 nmol/L). Reverse transcription–polymerase chain reaction of individually isolated afferent arterioles revealed the presence of message for EP₄ and all 3 EP₃ splice variants (, ß, and ) but not EP₁ or EP₂. Our findings thus indicate that PGE₂ elicits both vasodilatory and vasoconstrictor actions on the afferent arteriole. The vasodilation is mediated by EP₄ receptors coupled to cAMP, presumably via G_s. The vasoconstriction is mediated by an EP₃ receptor coupled to G_i and appears to reflect a functional antagonism of the EP₄-induced vasodilation.

Key Words: receptors • microcirculation • arterioles • cyclooxygenase • angiotensin II

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