Contribution of prostaglandin EP(2) receptors to renal microvascular reactivity in mice.

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