EFFECT OF RAPAMYCIN ON RAT AORTIC RING VASOMOTION

Rapamycin (PAPA) is an antifungal antibiotic with interesting new immu nosuppressive properties. We evaluated RAPA's effects in vitro on basa l and stimulated tension of isolated intact or denuded rat aortic ring s. Rings were prepared in an organ chamber and contracted with 40 mM K Cl (reference 100%). Some rings were treated with either RAPA's polyso rbate/polyethylene glycol-based (PEG) vehicle (0.8% vol/vol) or with d ifferent concentrations of RAPA (10, 100, and 1,000 ng/ml) diluted in PEG; untreated rings were used as controls. Variation in tension with time (2 h) and the dose-response to thromboxane A(2) analogue (U46619) and phenylephrine (PE) were measured in controls and treated rings. P EG potentiated the increase in basal tension in rings with endothelium after 2-h treatment (44.66 +/- 3.59 vs. 14.82 +/- 2.43% for controls, p < 0.05, n = 10). RAPA antagonized the contraction induced by its ow n vehicle dose dependently. At 1,000 ng/ml, PAPA caused relaxation of intact rings below the control level (4.29 +/- 2.20 vs. 14.82 +/- 2.43 %, p < 0.05, n = 10), but not in rings without endothelium. RAPA did n ot modify the response to PE or U46619 in rings with endothelium. PAPA relaxed the vessels by an endothelium-dependent mechanism, and this e ffect can be modulated by its vasoconstrictive PEG vehicle.