Aim: 

Despite the close association recognized between diabetes mellitus and vascular dysfunction, the mechanisms responsible for this association have not been clearly established. The purpose of the present study was to evaluate the effect of insulin-resistance syndrome on serotonin response in isolated aorta rings of lean Zucker (LZR) and obese Zucker rats (OZR), an animal model of insulin resistance.

Methods: 

Experiments were performed on 17-18-weeks old rats. Arterial rings were mounted in organ baths for isometric force recordings.

Results: 

The potency of serotonin in inducing contractions of isolated aorta were increased in segments from obese as compared with lean animals (pD2= 5.81 0.02; 5.53 0.04, n= 57 respectively; p < 0.001). Blockade of nitric oxide synthase markedly potentiated serotonin contractions in arteries from LZR but not from OZR. Conversely, oxygen reactive species removal and cyclooxygenase inhibition decreased the effect of serotonin in arteries from OZR but not from LZR. However, endothelin receptor blockade did not modify the serotonin response in both groups.

Conclusion: 

These findings suggest that insulin-resistance syndrome is associated with increased in vitro aorta reactivity to serotonin, which may account for a reduced NO function and increased level of free radicals in OZR. A minor contribution of a contractile prostanoid to the observed vascular dysfunction can not be ruled out.

This study has been supported by grant from Ministerio de Educación y Ciencia SAF2006-09191.