Therapy-Resistant Hypertension Associated with Central Obesity, Insulin Resistance, and Large Muscle Fibre Area

Obesity and an enhanced insulin response to oral glucose tolerance test are associated with therapy resistance in hypertension. In order to explore this association further we studied the insulin sensitivity of subjects with essential hypertension resistant to triple drug therapy (RH), with the euglycemic insulin clamp technique. Well controlled hypertensives, matched for age, gender and body mass index (BMI) served as controls. Male subjects (7 RH and 7 controls) were further investigated by biopsies of Musculus Vastus lateralis since structural conditions in skeletal muscles might have a role in the above association. Irrespective of pre-study drug therapy, therapy-resistant hypertensives had a lower insulin sensitivity index than controls (p < 0.05). In spite of the BMI-match waist/hip ratio (WHR) in the RH males tended to be higher (p < 0.07). Insulin clearance tended to be lower in RH subjects (p = 0.09). BMI correlated with a reduced muscular capillary density (r = -0.77, p < 0.01). The average cross-sectional muscle fibre area was larger in RH subjects (p < 0.05). The mean muscle fibre area correlated with basal serum insulin (r = 0.63; p < 0.05). Rarefaction of the muscular capillary bed appears to be related to obesity. Larger muscle fibres might be an effect of the growth factor properties of insulin and could possibly correspond to hypertrophy of smooth muscle in the resistance vessels. This factor might contribute to the association of hyperinsulinemia and hypertension and attenuate the response to antihypertensive therapy.