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Abstract: FR-OR079

Opposite Regulation of Renal and Cerebral Microarteriolar Angiotensin II Contractility by Specific Endothelial Prostaglandin Pathways

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms


  • Wilcox, Christopher S., Georgetown University Medical Center, Washington, District of Columbia, United States
  • Li, Lingli, Georgetown University, Washington, District of Columbia, United States
  • Lai, Enyin, Georgetown University, Washington, District of Columbia, United States
  • Welch, William J., Georgetown University, Washington, District of Columbia, United States

The kidney requires robust angiotensin II (Ang II) responsiveness for regulation of body fluids whereas the cerebral circulation requires resilience to Ang II to prevent cerebral ischemia and dementia. RNAseq of single cerebral microarterioles (CAs) versus renal afferent arterioles (Affs) detected >30-fold greater gene expression for COX2 and >3000-fold greater expression for lipokalin type prostaglandin D synthase (LPGDS) and DP1 receptor in CAs yet Affs expressed more thromboxane synthase. We reported enhanced contractility of Affs by thromboxane (Circulation research 94: 1436-1442, 2004). Therefore, we hypothesized that expression of different PGs accounts for regional differences in Ang II responsiveness.


Individual mouse microarterioles (8-15µm) from the intraparenchymal frontal cerebral cortex were compared to renal cortical Affs, perfused at 40 mmHg and change in diameter (%) assessed with Ang II (10-12 to 10-6 M).


Normal CAs were entirely unresponsive to 10-6 Ang II (0±0.03%) whereas Affs were highly responsive (-49±1 %). Ang II responses of CAs from COX1 -/- vs +/+ mice were enhanced (-15±2 vs 0±0.1% P<0.001) and enhanced further by COX2 blockade with parecoxib (-20±2 vs -15±2%; P<0.05) similar to effects of LPGDS blockade with AT56 in normal mouse arterioles (-15±4%). In contrast, COX-blockade reduced Ang II contractions of Affs. The DP1R agonist, BW450c reduced Ang II contractions of CAs from COX-blocked mice, yet was ineffective in Affs. Deendotheliaization of CAs enhances Ang II contractions in normal mouse CAs (0±0.1 vs 17.2±1.9%; P<0.001) but did not increase contractions further in COX-blocked CAs (19.8±1.5 vs 22.5±1.9%; NS).


The normal complete resilience of CAs to Ang II contractions depends on constitutive endothelial expression of COX1 and 2 and LPGDS generating vasodilator PGD2 that activates DP1 whereas the robust Ang II responsiveness of Affs is independent of PGD2 but depends on vasoconstrictor COX products. Thus, strong expression of PGD2 protects the cerebral circulation from ischemia with Ang II but strong expression of vasoconstrictor PGs renders the renal circulation highly Ang II responsive.


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