Interleukin-1 beta-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 synthas e (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-1 beta (IL-1 beta) in aortic rings of lean and obese Zucker rats, a model of experimental hyperinsulina emia. In order to modulate the insulin and glucose balance of the rats, a 2 2-week-long treadmill exercise was included in the study. The training atte nuated weight gain and reduced blood glucose in the obese and lean rats, wh ereas the abnormally high plasma insulin of the obese rats remained unaffec ted. A 6-h incubation of aortic rings with IL-1 beta (10 ng/ml) increased c yclic GMP in smooth muscle by approximately threefold in all groups, and th is effect was prevented by methylene blue. The contractile sensitivity of e ndothelium-denuded aortic rings to phenylephrine was reduced by incubation with IL-1 beta (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 ao rtic maximal contractile force induced by phenylephrine was reduced in sede ntary and exercised obese rats by incubation with IL-1 beta, while no chang e was detected in the lean rats. The aortic relaxation to exogenous L-argin ine was augmented by IL-1 beta in all groups, while the relaxation sensitiv ity to L-arginine after induction by IL-1 beta was enhanced by exercise in the obese but not in the lean rats. Finally, the relaxation to nitroprussid e was not significantly affected by IL-1 beta in any of the study groups. I n conclusion, since maximal contractile force generation to phenylephrine w as reduced by IL-1 beta in the obese but not in the lean rats, the sensitiv ity of NOS to induction by IL-1 beta was higher in arterial smooth muscle o f the obese than the lean Zucker rats. Thus, this model of hyperinsulinaemi a was not associated with reduced sensitivity of smooth muscle NOS to induc tion by IL-1 beta. Regular exercise did not change plasma insulin concentra tions, but it enhanced the action of insulin in both strains as reflected b y reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1 beta.