The α2-adrenoceptor agonists are widely applied in perioperative period because they have antinociceptive, sedative, anxiolytic, sympatholytic effects. With the development of investigation, the α2-adrenoceptor agon...The α2-adrenoceptor agonists are widely applied in perioperative period because they have antinociceptive, sedative, anxiolytic, sympatholytic effects. With the development of investigation, the α2-adrenoceptor agonists’ indications are expanded and have not been investigated as a kind of adjuvant. They will not only reduce anesthetic requirements during operation, cause sedation in ICU postoperatively, offer benefits in the prophylaxis of perioperative myocardial ischaemia but probably become some kind of anesthetic by themselves in perioperative application.展开更多
Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contract...Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α2-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α1-AR contractions involves interactions with α2-ARs in rat thoracic aortae. 1) Clonidine and guanfacine inhibited electrical field stimulation-induced contractions in a concentration-dependent, yohimbine-sensitive manner in isolated rat vas deferens preparations. 2) Clonidine almost completely suppressed phenylephrine-induced sustained contractions of rat thoracic aortae. 3) Clonidine competitively inhibited phenylephrine-induced contractions with a pA2 value of 6.77 at concentrations between 10-7 and 10-6 M. At 10-5 M, clonidine inhibited phenylephrine-induced contractions and dramatically reduced maximum contractions. 4) In contrast, clonidine did not inhibit contractions produced by high KCl or prostaglandin F2α. 5) Inhibition of phenylephrine-induced sustained contractions by clonidine was also produced in the presence of yohimbine. However, guanfacine did not inhibit phenylephrine-induced sustained contractions. These findings suggest that clonidine inhibits phenylephrine-induced contraction of rat thoracic aortae by competitive antagonism of α1-ARs, which is mediated through a mechanism independent of α2-AR stimulation.展开更多
Myocardial ischemia(MI)causes somatic referred pain and sympathetic hyperactivity,and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear.Here,in a rat model...Myocardial ischemia(MI)causes somatic referred pain and sympathetic hyperactivity,and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear.Here,in a rat model,we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back,but also elicited sympathetic sprouting in the skin of the referred area and C8–T6 dorsal root ganglia,and increased cardiac sympathetic tone,indicating sympathetic-sensory coupling.Moreover,intensifying referred hyperalgesic inputs with noxious mechanical,thermal,and electro-stimulation(ES)of the forearm augmented sympathetic hyperactivity and regulated cardiac function,whereas deafferentation of the left brachial plexus diminished sympathoexcitation.Intradermal injection of the α_(2) adrenoceptor(α_(2)AR)antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES.Overall,these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α_(2)AR-mediated sympathetic-sensory coupling.展开更多
文摘The α2-adrenoceptor agonists are widely applied in perioperative period because they have antinociceptive, sedative, anxiolytic, sympatholytic effects. With the development of investigation, the α2-adrenoceptor agonists’ indications are expanded and have not been investigated as a kind of adjuvant. They will not only reduce anesthetic requirements during operation, cause sedation in ICU postoperatively, offer benefits in the prophylaxis of perioperative myocardial ischaemia but probably become some kind of anesthetic by themselves in perioperative application.
文摘Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α2-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α1-AR contractions involves interactions with α2-ARs in rat thoracic aortae. 1) Clonidine and guanfacine inhibited electrical field stimulation-induced contractions in a concentration-dependent, yohimbine-sensitive manner in isolated rat vas deferens preparations. 2) Clonidine almost completely suppressed phenylephrine-induced sustained contractions of rat thoracic aortae. 3) Clonidine competitively inhibited phenylephrine-induced contractions with a pA2 value of 6.77 at concentrations between 10-7 and 10-6 M. At 10-5 M, clonidine inhibited phenylephrine-induced contractions and dramatically reduced maximum contractions. 4) In contrast, clonidine did not inhibit contractions produced by high KCl or prostaglandin F2α. 5) Inhibition of phenylephrine-induced sustained contractions by clonidine was also produced in the presence of yohimbine. However, guanfacine did not inhibit phenylephrine-induced sustained contractions. These findings suggest that clonidine inhibits phenylephrine-induced contraction of rat thoracic aortae by competitive antagonism of α1-ARs, which is mediated through a mechanism independent of α2-AR stimulation.
基金supported by the National Key R&D Program of China(2018YFC1704600)the National Natural Science Foundation of China(81674085,81904309).
文摘Myocardial ischemia(MI)causes somatic referred pain and sympathetic hyperactivity,and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear.Here,in a rat model,we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back,but also elicited sympathetic sprouting in the skin of the referred area and C8–T6 dorsal root ganglia,and increased cardiac sympathetic tone,indicating sympathetic-sensory coupling.Moreover,intensifying referred hyperalgesic inputs with noxious mechanical,thermal,and electro-stimulation(ES)of the forearm augmented sympathetic hyperactivity and regulated cardiac function,whereas deafferentation of the left brachial plexus diminished sympathoexcitation.Intradermal injection of the α_(2) adrenoceptor(α_(2)AR)antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES.Overall,these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α_(2)AR-mediated sympathetic-sensory coupling.
