Endothelin Receptor Blockade Blunts the Pressor Response to Acute Stress in Obese Men and Women.
Obesity is associated with dysregulation of the endothelin system. In obese individuals, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1. The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese individuals is unknown.


OBJECTIVE
To test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared to normal weight individuals.


METHODS
40 participants [Normal weight (NW): n=20, BMI: 21.7 ± 2.4 kg/m2 & Overweight/obese (OB): n=20, BMI: 33.8 ± 8.2 kg/m2] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment.


RESULTS
The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (p=0.039) in the OB group, compared to the NW group (OB: 28±12 vs LN: 34±15 mm Hg).


CONCLUSIONS
These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals.
['Derella|Cassandra C|CC|', 'Blanks|Anson M|AM|', 'Wang|Xiaoling|X|', 'Tucker|Matthew A|MA|', 'Horsager|Chase|C|', 'Jeong|Jin Hee|JH|', 'Rodriguez-Miguelez|Paula|P|', 'Looney|Jacob|J|', 'Thomas|Jeffrey|J|', 'Pollock|David M|DM|', 'Harris|Ryan A|RA|']
Obesity Endothelin-1 Bosentan Blood Pressure