A NEUROTENSIN RECEPTOR ANTAGONIST INHIBITS ACUTE IMMOBILIZATION STRESS-INDUCED CARDIAC MAST-CELL DEGRANULATION, A CORTICOTROPIN-RELEASING HORMONE-DEPENDENT PROCESS

Stress worsens certain disorders such as migraines or asthma, and has also been implicated in sudden myocardial arrest. it was previously sh own that acute psychological stress by immobilization results in dura mast cell degranulation, an effect blocked by pretreatment with antise rum against corticotropin-releasing hormone (CRH), Moreover, CRH was r ecently shown to induce skin mast cell degranulation. The effect of ps ychological stress was investigated on rat cardiac mast cells, because their release of coronary constrictive and proinflammatory molecules contributes to myocardial ischemia and possibly arrhythmias. Immobiliz ation of rats for 30 min induced maximal cardiac mast cell degranulati on as evidenced by light and electron microscopy. This effect was inhi bited by pretreatment with the ''antiallergic'' drug sodium cromoglyca te (cromolyn), which is thought to act primarily through mast cell sta bilization. Mast cell degranulation was also blocked by preincubation with antiserum against CRH and was partially inhibited by a CRH type-1 receptor selective antagonist. Sensory neuropeptides did not appear t o influence this effect, but a nonpeptide neurotensin receptor antagon ist blocked stress-induced cardiac mast cell degranulation. This findi ng supports the involvement of neuropeptide neurotensin which is prese nt in the heart and is known to trigger mast cell degranulation. These results indicate acute stress could result in local CRH and nonpeptid e neurotensin release which could contribute to myocardial pathophysio logy through direct or indirect release of cardiac mast cell mediators .