20-HETE and CYP4A2 ω-hydroxylase contribute to the elevated blood pressure in hyperandrogenemic female rats.

In this study we determined the roles of 20-HETE and CYP4A2 on the elevated BP in hyperandrogenemic female rats. Chronic dihydrotestosterone (DHT) increased mean arterial pressure (MAP) in female Sprague Dawley rats (96±2 vs 108±2 mmHg; p<0.05), and was associated with increased renal microvascular CYP4A2 mRNA expression (15 fold), endogenous renal 20-HETE (5 fold), and ω-hydroxylase activity (3 fold). Chronic DHT also increased MAP in low salt fed Dahl R females (81±4 vs 95±1 mmHg, p<0.05), but had no effect on MAP Dahl S (154±3 vs 153±3 mmHg) that are known to be 20-HETE deficient. To test the role of CYP4A2, female CYP4A2-/- and SS.5Bn (WT) rats were treated with DHT. DHT increased MAP in SS.5Bn (104±1 vs 128±1 mmHg; p<0.05), but had no effect in CYP4A2-/- females (118±1 vs 120±1 mmHg). Renal microvascular 20-HETE was reduced in CYP4A2-/- control females, and was increased with DHT in SS.5Bn females (6 fold), but not CYP4A2-/- females. ω-Hydroxylase activity was 40% lower in control CYP4A2-/- females than SS.5Bn, and DHT decreased ω-hydroxylase activity in SS.5Bn (by 50%), but significantly increased ω-hydroxylase activity in CYP4A2-/- females (3 fold). These data suggest that 20-HETE via CYP4A2 contributes to the elevation in BP in hyperandrogenemic females. The data also suggest that 20-HETE synthesis inhibition may be effective in treating the elevated BP in women with hyperandrogenemia, such as women with polycystic ovary syndrome. PMID: ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research