Effect of rapamycin on rat aortic ring vasomotion.
Rapamycin (RAPA) is an antifungal antibiotic with interesting new immunosuppressive properties. We evaluated RAPA's effects in vitro on basal and stimulated tension of isolated intact or denuded rat aortic rings. Rings were prepared in an organ chamber and contracted with 40 mM KCl (reference 100%). Some rings were treated with either RAPA's polysorbate/polyethylene glycol-based (PEG) vehicle (0.8% vol/vol) or with different 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 A2 analogue (U46619) and phenylephrine (PE) were measured in controls and treated rings. PEG 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 own vehicle dose dependently. At 1,000 ng/ml, RAPA 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 not modify the response to PE or U46619 in rings with endothelium. RAPA relaxed the vessels by an endothelium-dependent mechanism, and this effect can be modulated by its vasoconstrictive PEG vehicle.
Corbin
F
F
Department of Anaesthesiology, Notre-Dame Hospital, University of Montreal, Quebec, Canada.
Blaise
G A
GA
Parent
M
M
Chen
H
H
Daloze
P M
PM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001011:Aorta; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011090:Polyenes / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000378:metabolism / Q000494:pharmacology; D011136:Polysorbates / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D011090:Polyenes; D011136:Polysorbates; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D011092:Polyethylene Glycols; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D020123:Sirolimus