Muscarinic M2 Receptor Mediates Bradycardia and Hypotention Induced by Capsaicin Administration in the Rat

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Department of Life Science, NTNU


在我們最近一連串的研究中,給予大鼠辣椒素後會引起反射,促使呼吸暫停(apnea)、抑心(bradycardia)與降壓作用(hypotension),抑心效應可能是辣椒素引起的中樞反射作用,也有可能是直接作用於心肌細胞接受器。大鼠心肌細胞上有各種蕈鹼接受器亞型,活化M2會引起抑心與降壓作用,而活化M1則心跳變快、心肌收縮力增強。本實驗的目的是要研究蕈鹼接受器M2可能參與辣椒素處理後所引起的抑心與降壓作用。以Wistar雄性大鼠為實驗動物,腹腔注射urethane (1.2g/kg)麻醉後,進行氣管、股動脈插管及通向右心房入口的右頸靜脈插管。由微量注射針筒注射0.625與1.25μg/kg的辣椒素(i.v.),以引起心跳變慢與血壓下降,切斷迷走神經或投予非專一性蕈鹼接受器拮抗劑atropine(2.5與5 mg/kg,i.v.)可明顯降低辣椒素所誘發的抑心與降壓作用。預先處理M2接受器拮抗劑(gallamine triethiodide,0.4與l.6 mg/kg,i.v.),可有效阻斷辣椒素引起的抑心與降壓作用,但M1接受器拮抗劑(pirenzepine,12.5與50 μg/kg,i.v.)則無顯著影響。這些結果顯示,M2接受器確實參與辣椒素所誘發的抑心與降壓作用。
We have recently observed that capsaicin administration could produce cardiopulmonary chemoreflex reflex, characterized as apnea. bradcardia and hypotension. Bradycardia might be caused by a central-mediated reflex or by directly acting on receptors on the cardiac cells. There are varied muscarinic receptor subtypes on the cardiac cells. Activation of M2 receptors has been demonstrated to produce decreases in the heart rate while excitation of M1 receptors has been show ii to increase the heart rate. In the present study, we investigated whether muscarinic M2 receptors might centrally mediate the bradycardia and hypotension response caused by capsaicin-induced activation of pulmonary C-fibers. Male rats of the Wistar strain were used. A tracheostomy and a catherterization of the femoral artery w ere performed after anesthetization with urethane (1.2 g/kg, i.p.). Another catheter was advanced to close to the entrance of the atrium via the right jugular vein for capsaicin delivery. Capsaicin administration (0.625 and 1.25 μg/kg, i.v.) produced significant decreases in heart rate and blood pressure, which as substantially attenuated by the bilateral vagotomy or pretreatment of atropine (2.5 and 5 μg/kg, i.v.), a nonspecific muscarinic receptor antagonist. The bradycardia and hypotension caused by capsaicin administration was blocked by gallamine triethiodide (0.4 and 1.6 mg/kg, i.v.), an M2 receptor antagonist, but v as not blocked by the pretreatment of pirenzepine (12.5 and 50 μg/kg, i.v.), an M1 receptor antagonist. These results suggest that activation of M2 receptors might play a role in bradycardia and hypertension evoked by capsaicin-induced activation of pulmonary C-fibers.