Contribution of prostaglandin EP2receptors to renal microvascular reactivity in mice

The present studies were performed to determine the contribution of EP2receptors to renal hemodynamics by examining afferent arteriolar responses to PGE2, butaprost, sulprostone, and endothelin-1 in EP2receptor-deficient male mice (EP2−/−). Afferent arteriolar diameters averaged 17.8 ± 0.8 μm in wild-type (EP2+/+) mice and 16.7 ± 0.7 μm in EP2−/− mice at a renal perfusion pressure of 100 mmHg. Vessels from both groups of mice responded to norepinephrine (0.5 μM) with similar 17–19% decreases in diameter. Diameters of norepinephrine-preconstricted afferent arterioles increased by 7 ± 2 and 20 ± 6% in EP2+/+ mice in response to 1 μM PGE2and 1 μM butaprost, respectively. In contrast, afferent arteriolar diameter of EP2−/− mice decreased by 13 ± 3 and 16 ± 6% in response to PGE2and butaprost. The afferent arteriolar vasoconstriction to butaprost in EP2−/− mice was eliminated by angiotensin-converting enzyme inhibition. Sulprostone, an EP1and EP3receptor ligand, decreased afferent arteriolar diameter in both groups; however, the vasoconstriction in the EP2−/− mice was greater than in the EP2+/+ mice. Endothelin-1-mediated afferent arteriolar diameter responses were enhanced in EP2−/− mice. Afferent arteriolar diameter decreased by 29 ± 7% in EP2−/− and 12 ± 7% in EP2+/+ mice after administration of 1 nM endothelin-1. These results demonstrate that the EP2receptor mediates a portion of the PGE2afferent arteriolar vasodilation and buffers the renal vasoconstrictor responses elicited by EP1and EP3receptor activation as well as endothelin-1.