Biphasic Actions of Prostaglandin E<sub>2</sub>on the Renal Afferent Arteriole
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Bibliographic record
Abstract
Prostaglandin (PG) E(2) is an important modulator of the actions of angiotensin (Ang) II. In the present study, we investigated the renal microvascular actions of PGE(2) 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 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 vasodilation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and was mimicked by 11-deoxy-PGE(1) (0.01 to 1 nmol/L). Butaprost, which acts preferentially at EP(2) receptors, was relatively ineffective. Whereas 0.1 to 10 nmol/L PGE(2) elicited vasodilation, higher concentrations (1 to 10 micromol/L) restored Ang II-induced afferent arteriolar vasoconstriction. This response was blocked by pertussis toxin (200 microg/mL) and was mimicked by the EP(1)/EP(3) agonist sulprostone (1 to 300 nmol/L). Reverse transcription-polymerase chain reaction of individually isolated afferent arterioles revealed the presence of message for EP(4) and all 3 EP(3) splice variants (alpha, beta, and gamma) but not EP(1) or EP(2). Our findings thus indicate that PGE(2) elicits both vasodilatory and vasoconstrictor actions on the afferent arteriole. The vasodilation is mediated by EP(4) receptors coupled to cAMP, presumably via G(alphas). The vasoconstriction is mediated by an EP(3) receptor coupled to G(alphai) and appears to reflect a functional antagonism of the EP(4)-induced vasodilation.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it