Role of insulin preincubation in the contractile reactivity of rat aortic rings

Preincubation with physiological concentrations of insulin affects contract ile reactivity of isolated smooth muscle cells. We studied the effects of i nsulin on intact aortic rings of Wistar rats preincubated 1-2 h with 240 pM (I-1) and 960 pM (I-2) insulin with and without NO synthesis inhibition by N-omega-nitro-L-arginine methyl ester (L-NAME). Resting force was tripled by 0.1 mM L-NAME in control (C) and I-1 groups, but not in I-2 groups. I-1 treatment decreased the tachyphylaxis to two successive 1 mu M arginine vas opressin (AVP) stimulations. Single contractions elicited by 1 mu M AVP, 1 mu M angiotensin II (AngII), or 0.01 mu M endothelin (ET1) were not affecte d by insulin preincubation in either maximal force (F-max) or relaxation ti mes. L-NAME enhanced F-max of AngII contractions by about 75% in C, 120% in I-1, and 74% in I-2 groups; accordingly, it augmented the final steady-sta te force in C and I-1 but not in It. Similarly, L-NAME increased F-max (30- 40%) of AVP and ET1 contractions in C and I-1 groups but failed to do so in contractions of I-2 group. Results obtained with 10 mu M indomethacin sugg est that this is due to insulin stimulation of prostacyclin effects.