Blood Pressure Decrease Induced By Low Dose Epinephrine Via Different Routes In Rats And The Mechanism

Epinephrine is the most widely used vasoactive drug in clinic. Usual doses of epinephrine intravenous injection can increase blood pressure and enhance myocardial contractility which is used in some life-threatening circumstances, including the treatment of cardiac arrest, circulatory collapse, and anaphylaxis. Recently, there were many reports indicated that epinephrine nasal or scalp infiltration or endotracheal administration could induce a significant blood pressure decrease. However the putative mechanism of the blood pressure decrease remains uncertainEpinephrine activates all adrenergic receptors. The hemodynamic effects of epinephrine are variable and are related to blood levels which are dose dependent. Doses of1to2μg/min predominantly activate β2-receptors with resulting vascular and bronchial smooth muscle relaxation. Doses of2to10μg/min increase heart rate, contractility, and conduction by activating β2-receptors. Doses in excess of10μg/min cause marked a-adrenergic stimulation with resultant generalized vasoconstriction.We theorized the blood pressure decrease to the stimulation of (32-receptor with resulting vascular smooth muscle and the decrease in peripheral vascular resistance, while the selective β2-adrenoceptors antagonist can not be applied to clinic research. The present studies including two consecutive but relative independent parts were designed to establish the model of decreased blood pressure after different routes of low dose epinephrine injection in rats and to investgiate the putative mechanism. Section1:Blood pressure decrease induced by low dose epinephrine via different routes in rats1. Blood pressure decrease induced by low dose epinephrine intranasal infiltration in ratsAbstract Objective This study was to observe the hemodynamic effects of epinephrine intranasal infiltration in rats. Methods Sixteen Sprague-Dawley male rats weighing350-400g were equally randomized into epinephrine group and saline group (n=8), and scheduled to intranasal infiltrated with either epinephrine (1:100,000)0.2mL or equal volume of saline. Mean arterial pressure (MAP), and heart rate (HR) were recorded before infiltration (baseline) and at1,2,3,4,5,6,7,8,9,10min after infiltration. Results Compared with the baseline, MAP decreased from3min to10min after epinephrine infiltration (P<0.05), while HR had no significently changes in this period. Conclusion Epinephrine (1:100,000)0.2mL intranasal infiltration can induce significant blood pressure decrease in rats.2. Effects of different doses of epinephrine intravenous injection on blood pressure in ratsObjective This study was to investigate the effects of different doses of epinephrine intravenous injection on blood pressure in rats and explore the possible mechanism. Methods Forty Sprague-Dawley male rats, weighing350-400g, were equally randomized into5groups (n=8). Groups E1-4were intravenously injected with epinephrine0.125μg/kg,0.25μg/kg,0.5μg/kg and1μg/kg, respectively. Group S were intravenously injected with equal volume of saline. MAP and HRwere recorded before epinephrine or saline injection (basline, T0) and5,10,15,30s and1,2,3,4,5min (T1-9) after intravenous injection. Results MAP had no significant difference in all groups at To. Compared with To, MAP has no significant change at all time points in group E1. MAP decreased at T2-5in group E2while increased at T1and decreased at T3,4in group E3while increased at T1-7in group E4(P<0.5). HR increased at T1-6in group E4and had no significant change in the other groups at all time points. Conclusion Epinephrine intravenous injection in rats can cause decreased MAP in a low dose and biphasic changes of MAP in a moderate dose and increased MAP in a large dose.3. Blood pressure decrease induced by low dose epinephrine aortic injection in ratsObjective This study was to investigate the hemodynamic effects after low dose epinephrine aortic injection in rats. Methods Sixteen Sprague-Dawley male rats were equally randomized into epinephrine group and saline group (n=8), and scheduled to received epinephrine0.1μg/kg and equal volume of saline from aorta, respectively. MAP) and HR were recorded before aortic injection (T0)and5、10、15、20、30s and1、1.5、2、2.5、3、4、5min (T1-11) after aortic injection. Results Compared with To, MAP decreased at T2-5and returned to the baseline at T6in epinephrine group (P<0.05). There was no significant change in HR in the two groups at every time points. Conclusion Epinephrine0.1μg/kg aortic injection can result in transient but significant blood pressure decrease in rats. Section2:Effects of β2-adrenoceptors antagonist ICI118551on blood pressure after low dose epinephrine via different routes injection in rats1. β2-adrenoceptors antagonist ICI118551prevents the blood pressure decrease induced by epinephrine intranasal infiltration in ratsObjective To investigate the effects of β2-adrenoceptors antagonist ICI118551on blood pressure after low dose epinephrine intranasal infiltration in rats. Methods Thirty-two Sprague-Dawley male rats were equally randomized into4groups (n=8):saline+saline group (S group), ICI118551+saline group (I group), saline+epinephrine group (E group), and ICI118551+epinephrine group (IE group). Rats received intravenous injection of saline0.2mL (S group and I group) or ICI1185510.5mg/kg (I group and IE group). Twenty minutes later, rats received intranasal infiltration of saline (S group and I group) or epinephrine (E group and IE group, concentration of1:100000)0.2mL. E group and IE group were intravenously injected with saline0.2mL or ICI1185510.5mg/kg20min before intranasal infiltration with2μg epinephrine (0.2mL), respectively. Mean arterial pressure (MAP) and heart rate (HR) were recorded before infiltration (basline) and1,2,3,4,5,6,7,8,9and10min after intranasal initiation. Results Compared with basline, MAP decreased from3min to10min in E group while increased at6min and7min in IE group (P<0.05). There was no significant change in HR in all groups. Conclusion Epinephrine2μg intranasal infiltration can induce blood pressure decrease in rats and pretreatment with ICI118551can prevent this blood pressure decrease.2. β2-adrenoceptors antagonist ICI118551prevents the blood pressure decrease induced by epinephrine intravenous injection in ratsObjective:To investigate the effects of β2-adrenoceptors antagonist ICI118551on blood pressure after epinephrine intravenous injection in rats. Methods: Thirty-two Sprague-Dawley male rats were equally randomized into4groups (n=8): saline+saline group (S group), ICI118551+saline group (I group), saline+epinephrine group (E group), and ICI118551+epinephrine group (IE group). S group and I group were intravenously injected with saline0.2ml or ICI1185510.5mg/kg 20min before intravenous injection with0.2ml saline, respectively. E group and IE group were intravenously injected with saline0.2ml or ICI1185510.5mg/kg20min before intravenous injection with0.25μg/kg epinephrine (0.2ml), respectively. Mean arterial pressure (MAP) and heart rate (HR) were recorded before intravenous injection (baseline, To) and5,10,15,30s and1,2,3,4,5min (T1-9) after intravenous application. Results:Compared with To, MAP decreased at T2-5and returned to the baseline at T6in E group (P<0.5). MAP had no significant change in other groups at all time points. There was no remarkably change in HR in all groups. Conclusion: β2-adrenoceptors antagonist ICI118551can prevent the blood pressure decrease induced by epinephrine0.25μg/kg intravenous injection in rats.3. β2-adrenoceptors antagonist ICI118551prevents the blood pressure decrease induced by epinephrine aortic injection in ratsObjective:To investigate the effects of β2-adrenoceptors antagonist ICI118551on blood pressure after epinephrine aortic injection in rats. Methods: Thirty-two Sprague-Dawley male rats were equally randomized into4groups (n=8): saline+saline group (S group), ICI118551+saline group (I group), saline+epinephrine group (E group), and ICI118551+epinephrine group (IE group). S group and I group were intravenously injected with saline0.2ml or ICI1185510.5mg/kg20min before aortic injection with0.2ml saline, respectively. E group and IE group were intravenously injected with saline0.2ml or ICI1185510.5mg/kg20min before aortic injection with0.1μg/kg epinephrine (0.2ml), respectively. Mean arterial pressure (MAP) and heart rate (HR) were recorded before aortic injection (baseline, To) and5,10,15,20,30s and1,1.5,2,2.5,3,4,5min (T1-11) after aortic application. Results:Compared with To, MAP decreased at T2-5and returned to the baseline at T6in E group (P<0.5). MAP had no significant change in other groups at all time points. There was no remarkably change in HR in all groups. Conclusion: β2-adrenoceptors antagonist ICI118551can prevent the blood pressure decrease induced by epinephrine0.1μg/kg aortic injection in rats. SummaryEpinephrine intranasal infiltration and injected from femoral vein or aorta can result in significant blood pressure decrease in rats. The scale and the duration time of the blood pressure decrease are not the same. Epinephrine intranasal infiltration can induce a prolonged decrease in blood pressure which may be a putative explanation to the sustained-absorption of epinephrine from the nasal mucosa in rats. Epinephrine injected from femoral vein or aorta can induce a transient blood pressure decrease, which may be related to the different injection approachs of epinephrine circulating in the blood. Epinephrine intravenous injection in rats can cause decreased blood pressure in a low dose and biphasic changes of blood pressure in a moderate dose and increased blood pressure in a large dose. This may be relevant to activation of different adrenoceptors.The epinephrine-induced blood pressure decrease can be effectively prevented by β2-adrenoceptors antagonist ICI118551which indicates that the putative mechanism of epinephrine-induced decrease in blood pressure is the activation of β2-adrenoceptors mediating peripheral vasodilatation effects.