Direct vasoconstrictor effect of prostaglandin E₂on renal interlobular arteries: role of the EP3 receptor

Abstract

van Rodijnen WF, Korstjens IJ, Legerstee N, ter Wee PM, Tangelder GJ. Direct vasoconstrictor effect of prostaglandin E 2 on renal interlobular arteries: role of the EP3 receptor. Am J Physiol Renal Physiol 292: F1094 -F1101, 2007. First published December 5, 2006; doi:10.1152/ajprenal.00351.2005.-Evidence indicates that prostaglandin E2 (PGE2) preferentially affects preglomerular renal vessels. However, whether this is limited to small-caliber arterioles or whether larger vessels farther upstream also respond to PGE2 is currently unclear. In the present study, we first investigated the effects of PGE 2 along the preglomerular vascular tree and subsequently focused on proximal interlobular arteries (ILAs). Proximal ILAs in hydronephrotic rat kidneys as well as isolated vessels from normal kidneys constricted in response to PGE2, both under basal conditions and after the induction of vascular tone. By contrast, smaller vessels, i.e., distal ILAs and afferent arterioles, exhibited PGE2-induced vasodilation. Endothelium removal and pretreatment of single, isolated proximal ILAs with an EP1 receptor blocker (SC51322, 1 mol/l) or a thromboxane A2 receptor blocker (SQ29548, 1 mol/l) did not prevent vasoconstriction to PGE2. Furthermore, in the presence of SC51322, responses of these vessels to PGE2 and the EP1/EP3 agonist sulprostone were superimposable, indicating that PGE2-induced vasoconstriction is mediated by EP3 receptors on smooth muscle cells. Immunohistochemical staining of proximal ILAs confirmed the presence of EP3 receptor protein on these cells and the endothelium. Adding PGE2 to normal isolated kidneys induced a biphasic flow response, i.e., an initial flow increase at PGE2 concentrations Յ0.1 mol/l followed by a flow decrease at 1 mol/l PGE2. Thus our results demonstrate that PGE2 affects multiple segments of the preglomerular vascular tree in a different way. At the level of the proximal ILAs, PGE2 had a direct vasoconstrictor action mediated by EP3 receptors. interlobular arteries; vasoconstriction PGE 2 IS ONE OF the major cyclooxygenase-derived products produced by the kidney (17). The actions of PGE 2 intrarenally include both tubular and vascular effects (2). The latter are important for regulating renal function under various circumstances. So far, the effects of PGE 2 on smaller pre-and postglomerular arterioles have mainly received attention. The postglomerular efferent arterioles were found to be insensitive to PGE 2 (4, 23), while for the preglomerular afferent arterioles (AAs) and distal interlobular arteries (ILAs) most studies indicated vasodilation (4,8,23), although vasoconstriction in certain instances has been reported as well (9, 23). Whether larger vessels further upstream of the glomerulus are also sensitive to PGE 2 is currently unknown. Previous studies have demonstrated that larger preglomerular vessels constrict in response to inflammatory mediators, such as serotonin and leukotrienes (5, 19), suggesting a similar mode of action for PGE 2 .In general, the actions of PGE 2 are m...

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“…Those studies that have been reported have mainly employed the hydronephrotic kidney model, which allows direct visualization of nearly the entire renal microvasculature, albeit in a chronically nonfiltering and remodeled kidney. For example, van Rodijnen and colleagues (31) recently showed that proximal interlobular arteries constrict in response to prostaglandin E2, whereas downstream vascular elements tend to dilate.…”

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“…EP 3 agonists have been shown to reduce infarct size and reduce myocardial injury (Zacharowski et al, 1999;Hohlfeld et al, 2000), with supportive evidence from cardiospecific EP 3 receptor overexpression . In the kidney, an EP 3 vasoconstrictor effect has been observed for the intralobular arteries (van Rodijnen et al, 2007).…”

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“…PGE 2 has also been reported to elicit vasoconstriction in a variety of arterial segments, including cerebral arteries. 110–112 The direct effect of PGE 2 on parenchymal arteriolar tone and its mechanism of action requires further investigation.…”