Effect of high‐fat diet (HFD) on resistance artery function in normal pregnant rats

Abstract

Despite clinical evidence that obesity is the leading attributable risk for preeclampsia (PE) in developed countries, the mechanisms whereby metabolic factors increase the risk for PE are unclear. The purpose of this study was to examine the effects of HFD on resistance artery endothelial function in normal pregnant rats. Twelve‐week‐old Sprague‐Dawley rats were fed a normal diet (ND; 13% fat kcal; N=5–8) or HFD (40% fat kcal; N=9–11). At 21 weeks old, timed‐pregnant rats were generated. At gestational day 19, wire myography showed in third‐order mesenteric arteries that sensitivity (logEC50) of endothelial‐dependent relaxation to acetylcholine (ACh) was greater in HFD (−7.9 ± 0.3M) vs. ND (−6.7 ± 0.3M) (P<0.05). In the HFD group, treatment of artery rings with the non‐selective nitric oxide synthase inhibitor L‐NAME reduced sensitivity to ACh (logEC50 of −6.6 ± 0.2M, P<0.05 vs. untreated rings), whereas in the ND group, L‐NAME did not alter the ACh response (−6.6 ± 0.3M) vs. untreated rings. Endothelial‐independent relaxation to Na nitroprusside was similar (logEC50: ND: −6.5 ± 0.4M vs. HFD: −7.0 ± 0.2M). These data suggest that normal pregnancy protects against HFD‐induced endothelial dysfunction. However, this protective pathway may be targeted in PE by factors released from the ischemic placenta that are known to promote the hypertension and endothelial dysfunction of this disease. HL105324, HL51971