Obese melanocortin‐4 receptor‐deficient rats exhibit attenuated adrenergic vasoconstriction (1084.2)

Abstract

Preeclampsia is a hypertensive disorder of pregnancy associated with placental ischemia‐induced endothelial dysfunction and exaggerated vasoconstriction. Obesity is a major risk factor for the development of preeclampsia but the mechanisms are unclear. Intriguingly, we previously showed that obese MC4R heterozygous (+/‐) rats not subjected to placental ischemia are normotensive with augmented endothelial‐dependent relaxation and smooth muscle relaxation response to a nitric oxide donor. To further examine vascular function in obese pregnancy, we tested the hypothesis that obese MC4R +/‐ pregnant rats have attenuated vasoconstriction. At gestational day 19, third‐order mesenteric arteries were isolated from obese MC4R +/‐ (N=6) and lean MC4R +/+ (N=10) rats and mounted in a wire myograph. Sensitivity (logEC50) to vasoconstriction induced by phenylephrine (PE) was significantly (P<0.05) reduced in obese (‐4.9±0.3M) vs. lean (‐5.6±0.1M) pregnant rats whereas the maximum contractile response (% increase in force) to PE was similar between obese (241±57%) and lean (305±49%) pregnant groups. Vasoconstriction stimulated by depolarization to KCl was similar between obese vs. lean rats: EC50 (56.5±2.9mM vs. 48.1±1.3mM) or maximum response (150±13% vs. 168±13%). In conclusion, these data indicate that pregnancy in obese MC4R +/‐ rats is associated with reduced adrenergic vasoconstriction. However, we speculate that adrenergic vasoconstriction may be exaggerated in obese pregnant animals with placental ischemia‐induced endothelial dysfunction.Grant Funding Source: Supported by HL105324, HL51971.