Objective: 

Patients with obesity have an increased risk for cardiovascular disease, possibly related to endothelial-dysfunction. This study investigates the acetylcholine mediated relaxation in subcutaneous resistance arteries from obese patients (BMI > 40) undergoing gastric-bypass operation or undergoing surgery for non-cardiovascular related reasons (i.e. kidney transplant donors).

Methods: 

Arteries dissected from biopsies taken from 12 control and 12 obese matched for age and sex were mounted in an isometric myograph. Endothelium-dependent relaxation was investigated by increasing concentrations of acetylcholine on noradrenaline pre-contracted vessels. The EDHF-like response was investigated in the presence of eNOS and COX inhibitors and pharmacological modulators of the pathways involved in the EDHF response.

Results: 

There was no difference between the groups in maximal relaxation under control conditions (86±6 and 89±3%, obese and control, respectively). However, the sensitivity to acetylcholine was significantly higher in obese (logEC50 was -7.4±0.1and -7.1±0.1, obese and control, respectively (P=0.02)). Also after blocking eNOS and COX the sensitivity to acetylcholine was higher in obese (logEC50 -6.6±0.1 and -6.2±0.1 (P=0.02)) while maximal relaxation was not different (61±9 and 70±4% (P>0.5), obese and control, respectively). Treatment with the IK and SK channel opener NS309 (1mM) abolished the difference in sensitivity (logEC50 -7.3±0.1 and -7.2±0.2) while increasing maximal relaxation (77±4 and 79±14%, n= 11 and 3) obese and control, respectively.

Conclusions: 

Subcutaneous resistance arteries from obese patients seem to have increased sensitivity to the endothelial specific vasodilator acetylcholine, also after blockade of the eNOS and COX dependable pathways.