Interleukin-1β-induced nitric oxide synthesis in aortic rings from normal and hyperinsulinaemic rats: effect of physical exercise

Insulin has been suggested to prevent the induction of nitric oxide synthase (NOS) in vitro in arterial smooth muscle, but whether such a mechanism is operative in vivo is not known. Therefore, we evaluated the sensitivity of smooth muscle NOS to induction by interleukin-1β (IL-1β) in aortic rings of lean and obese Zucker rats, a model of experimental hyperinsulinaemia. In order to modulate the insulin and glucose balance of the rats, a 22-week-long treadmill exercise was included in the study. The training attenuated weight gain and reduced blood glucose in the obese and lean rats, whereas the abnormally high plasma insulin of the obese rats remained unaffected. A 6-h incubation of aortic rings with IL-1β (10 ng/ml) increased cyclic GMP in smooth muscle by approximately threefold in all groups, and this effect was prevented by methylene blue. The contractile sensitivity of endothelium-denuded aortic rings to phenylephrine was reduced by incubation with IL-1β (1 ng/ml and 10 ng/ml) in the exercised obese and lean rats, whereas no significant change was observed in the sedentary groups. The aortic maximal contractile force induced by phenylephrine was reduced in sedentary and exercised obese rats by incubation with IL-1β, while no change was detected in the lean rats. The aortic relaxation to exogenous L-arginine was augmented by IL-1β in all groups, while the relaxation sensitivity to L-arginine after induction by IL-1β was enhanced by exercise in the obese but not in the lean rats. Finally, the relaxation to nitroprusside was not significantly affected by IL-1β in any of the study groups. In conclusion, since maximal contractile force generation to phenylephrine was reduced by IL-1β in the obese but not in the lean rats, the sensitivity of NOS to induction by IL-1β was higher in arterial smooth muscle of the obese than the lean Zucker rats. Thus, this model of hyperinsulinaemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1β. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1β.