Restraint stress exacerbates cardiac and adipose tissue pathology via β-adrenergic signaling in rats with metabolic syndrome.

Restraint stress stimulates sympathetic nerve activity and can affect adiposity and metabolism. However, the effects of restraint stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We investigated the effects of chronic restraint stress and β-adrenergic receptor (β-AR) blockade on cardiac and adipose tissue pathology and metabolic disorders in a rat model of MetS. DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats. Rats were exposed to restraint stress (restraint cage, 2 h/day) for 4 wk from 9 wk of age with or without daily subcutaneous administration of the β-AR blocker propranolol (2 mg/kg). Age-matched homozygous lean littermates of DS/obese rats (DahlS.Z-Lepr(+)/Lepr(+) rats) served as control animals. Chronic restraint stress exacerbated hypertension as well as left ventricular hypertrophy, fibrosis, diastolic dysfunction, and oxidative stress in a manner sensitive to propranolol treatment. Restraint stress attenuated body weight gain in DS/obese rats, and this effect tended to be reversed by propranolol (P = 0.0682). Restraint stress or propranolol did not affect visceral or subcutaneous fat mass. However, restraint stress potentiated cardiac and visceral adipose tissue inflammation in DS/obese rats, and these effects were ameliorated by propranolol. Restraint stress also exacerbated glucose intolerance, insulin resistance, and abnormal lipid metabolism in a manner sensitive to propranolol. In addition, restraint stress increased urinary norepinephrine excretion, and propranolol attenuated this effect. Our results thus implicate β-ARs in the exacerbation of cardiac and adipose tissue pathology and abnormal glucose and lipid metabolism induced by restraint stress in this model of MetS.