| First Author | Ding Y | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 5 | Pages | F753-63 |
| PubMed ID | 23825080 | Mgi Jnum | J:200931 |
| Mgi Id | MGI:5510282 | Doi | 10.1152/ajprenal.00292.2013 |
| Citation | Ding Y, et al. (2013) 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension. Am J Physiol Renal Physiol 305(5):F753-63 |
| abstractText | 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented 5alpha-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14(-/-) mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 +/- 1 vs. 15 +/- 1 mum) and M/L (0.29 +/- 0.03 vs. 0.17 +/- 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12-20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 +/- 4 vs. 92 +/- 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 +/- 1 vs. 16 +/- 1 mum; M/L: 0.39 +/- 0.04 vs. 0.23 +/- 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. |
