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Hypertension, often referred to as ‘The silent killer’, is christened so, as it is seldom preceded by any warning signs or symptoms. With the new ACC/AHA guidelines lowering the Blood Pressure (BP) threshold values, it has resulted in a 140% relative increase in the hypertension prevalence in India, which is 3 times higher than that of in United States. Imidazoline receptor agonists control BP effectively with minimal adverse effects of sedation and mental depression that are usually associated with centrally acting antihypertensives. While having a low affinity to the α2-adrenergic receptors, these new generation centrally acting antihypertensive agents are highly selective for imidazoline receptor. Moxonidine, a second-generation centrally acting antihypertensive drug having selective agonist activity on imidazoline I1 receptors and minor activity on imidazoline α2 adrenoceptors, reduces the activity of Sympathetic Nervous System (SNS) by activating I1 imidazoline receptors in Rostral Ventrolateral Medulla (RVLM). Studies of moxonidine have shown equal effectiveness in lowering BP like other well-established antihypertensive drugs such as nifedipine, atenolol or angiotensin-converting enzyme inhibitors, with minimal adverse events. At doses of 0.2-0.6 mg, moxonidine induces satisfactory BP reduction in patients with mild-to-moderate essential hypertension. In patients with mild-to-moderate hypertension, moxonidine (0.2-0.4 mg o.d.) significantly decreased Systolic Blood Pressure/Diastolic Blood Pressure (SBP/DBP), respectively, by 19.5/11.6 mmHg. In obese, non-controlled hypertensive patients, there is a 14% and 13.5% reduction in the mean SBP and DBP, respectively, from the baseline value after moxonidine treatment and during the follow-up with an additional reduction in body weight, plasma leptin levels and Body Mass Index (BMI) (p<0.01). Thus, moxonidine could be considered as a therapeutic option in obese patients with metabolic syndrome.
ABSTRACT
Objective: Clonidine, by activating peripheral α-adrenoceptors, produces transient pressor response after i. v. injection in anesthetized animals. Moxonidine, with at least 40-fold higher affinity to I1-imidazoline receptors than to α2-adrenoceptors, produces also a transient pressor response. This work was designed to investigate whether I1-imidazoline receptors are involved in this pressor effect of moxonidine. Methods: Female spontaneously hypertensive rats (SHRs, aged 14-16 weeks) were anesthetized with urethane. To observe the transient pressor responses, moxonidine 0. 1, 0. 3, 1. 0 mg/kg (intravenous, i. v.), 2.0 μg (intracerebroventricular, i. c. v.) and 1.0, 10.0 mg/kg (intragastric, i. g.) were administrated in different groups of rats. To evaluate the roles of α1-adrenoceptors, α2-adrenoceptors and I1-imidazoline receptors in the transient pressor responses to moxonidine, prazosin (10.0 μg/kg), yohimbine (2.0 mg/kg), phentolamine (0.2 mg/kg), idazoxan (1.0 mg/kg) or yohimbine + idazoxan (2.0 mg/kg + 1.0 mg/kg) were intravenously given to the animals before moxonidine 0.3 mg/kg i. v.). Results: It was found that i. v. moxonidine produced a greater pressor response than clonidine when producing a similar reduction of blood pressure. This effect of moxonidine was not influenced by prazosin, but was partly inhibited by yohimbine, phentolamine or idazoxan, and completely blocked by the combination of yohimbine and idzaxon. Neither i. c. v. injection nor i. g. administration of moxonidine induced transient pressor responses. Conclusion: The transient pressor response of i. v. moxonidine is mediated by both peripheral I1-imidazoline receptors and α2-adrenoceptors.
ABSTRACT
Objective:Clonidine,by activating peripheral α-sbrenoceptors, produces transient pressor response after i.v.injection in anesthetized animals.Moxonidine, with at least 40-fold higher affinity to I1-imidazoline receptors than to α2-adrenoceptors,produces also a transient pressor response. This work was designed to investigate whether I1-imidazoline receptors are involved in this pressor effect of moxonidine. Methods:Female spontaneously hypertensive rats(SHRs,aged 14-16 weeks)were anesthetized with urethane.To observe the transient pressor responses,moxonidine 0.1,0.3,1.0mg/kg(intravenous,i.v),2.0μg(intracerebroventricular,i.c.v.)and 1.0,10.0mg/kg(intragastric,i.g.)were administrated in different groups of rats.To evaluate the roles of α1-adrenoceptors,α2-adrenoceptors and I1-imidazoline receptors in the transient pressor responses to moxonidine, prazosin(10.0μg/kg),yohimbine(2.0mg/kg),phentolamine(0.2mg/kg),idazoxan(1.0mg/kg)or yohimbine+idazoxan(2.0mg/kg+1.0mg/kg)were intravenously given to the animals before moxonidine 0.3mg/kg (i.v.).Results:It was found that i.v.moxonidine produced a greater pressor response than clonidine when producing a similar reduction of blood pressure.This effect of moxonidine was not influenced by prazosin, but was partly inhibited by yohimbine, phentolamine or idazoxan,and completely blocked by the combination of yohimbine and idzaxon.Neither i.c.v.injection nor i.g. administration of moxonidine induced transient pressor responses.Conclusion:The transient pressor response of i.v. moxonidine is mediated by both peripheral I1-imidazoline receptors and α2-adrenoceptors.
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Objective:Clonidine,by activating peripheral α-sbrenoceptors, produces transient pressor response after i.v.injection in anesthetized animals.Moxonidine, with at least 40-fold higher affinity to I1-imidazoline receptors than to α2-adrenoceptors,produces also a transient pressor response. This work was designed to investigate whether I1-imidazoline receptors are involved in this pressor effect of moxonidine. Methods:Female spontaneously hypertensive rats(SHRs,aged 14-16 weeks)were anesthetized with urethane.To observe the transient pressor responses,moxonidine 0.1,0.3,1.0mg/kg(intravenous,i.v),2.0μg(intracerebroventricular,i.c.v.)and 1.0,10.0mg/kg(intragastric,i.g.)were administrated in different groups of rats.To evaluate the roles of α1-adrenoceptors,α2-adrenoceptors and I1-imidazoline receptors in the transient pressor responses to moxonidine, prazosin(10.0μg/kg),yohimbine(2.0mg/kg),phentolamine(0.2mg/kg),idazoxan(1.0mg/kg)or yohimbine+idazoxan(2.0mg/kg+1.0mg/kg)were intravenously given to the animals before moxonidine 0.3mg/kg (i.v.).Results:It was found that i.v.moxonidine produced a greater pressor response than clonidine when producing a similar reduction of blood pressure.This effect of moxonidine was not influenced by prazosin, but was partly inhibited by yohimbine, phentolamine or idazoxan,and completely blocked by the combination of yohimbine and idzaxon.Neither i.c.v.injection nor i.g. administration of moxonidine induced transient pressor responses.Conclusion:The transient pressor response of i.v. moxonidine is mediated by both peripheral I1-imidazoline receptors and α2-adrenoceptors.
ABSTRACT
Objective:Clonidine,by activating peripheral α-sbrenoceptors, produces transient pressor response after i.v.injection in anesthetized animals.Moxonidine, with at least 40-fold higher affinity to I1-imidazoline receptors than to α2-adrenoceptors,produces also a transient pressor response. This work was designed to investigate whether I1-imidazoline receptors are involved in this pressor effect of moxonidine. Methods:Female spontaneously hypertensive rats(SHRs,aged 14-16 weeks)were anesthetized with urethane.To observe the transient pressor responses,moxonidine 0.1,0.3,1.0mg/kg(intravenous,i.v),2.0μg(intracerebroventricular,i.c.v.)and 1.0,10.0mg/kg(intragastric,i.g.)were administrated in different groups of rats.To evaluate the roles of α1-adrenoceptors,α2-adrenoceptors and I1-imidazoline receptors in the transient pressor responses to moxonidine, prazosin(10.0μg/kg),yohimbine(2.0mg/kg),phentolamine(0.2mg/kg),idazoxan(1.0mg/kg)or yohimbine+idazoxan(2.0mg/kg+1.0mg/kg)were intravenously given to the animals before moxonidine 0.3mg/kg (i.v.).Results:It was found that i.v.moxonidine produced a greater pressor response than clonidine when producing a similar reduction of blood pressure.This effect of moxonidine was not influenced by prazosin, but was partly inhibited by yohimbine, phentolamine or idazoxan,and completely blocked by the combination of yohimbine and idzaxon.Neither i.c.v.injection nor i.g. administration of moxonidine induced transient pressor responses.Conclusion:The transient pressor response of i.v. moxonidine is mediated by both peripheral I1-imidazoline receptors and α2-adrenoceptors.
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0.05). CONCLUSION: The effects of 10 mg?kg -1 m oxonidine on reduced blood pressure and heart rate in SHR is equal to the effect s of 1 mg?kg -1 clonidine after once large dose oral administration. T here is no significant difference between the moxonidine and clonidine of the sa me dose in reducing blood pressure after repeatedly small dose oral administrati on in SHR.
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Aim To investigate effects of moxonidine on hemodynamics in anesthetized rats. Methods The indexes of hemodynamics were examined by catheterization of arteries in anesthetized Wistar rats. Results DBP, +dp/dt_ max, -dp/dt_ max,t-dp/dt_ max ,V_ pm and V_ max were significantly declined in dose-dependent manner after administration, but HR and SBP didn't change significantly. Conclusion These results showed that antihypertensive effects of moxonidine were related to inhibition of systolic and diastolic functions of myocardium.Furthermore,the antihypertensive effects of moxonidine were associated with reduction of peripheral vascular resistance.
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Objective:Clonidine,by activating peripheral?-adrenoceptors,produces transient pressor response after i.v. injection in anesthetized animals.Moxonidine,with at least 40-fold higher affinity to I_1-imidazoline receptors than to?_2-adreno- ceptors,produces also a transient pressor response.This work was designed to investigate whether I_1-imidazoline receptors are involved in this pressor effect of moxonidine.Methods:Female spontaneously hypertensive rats(SHRs,aged 14-16 weeks) were anesthetized with urethane.To observe the transient pressor responses,moxonidine 0.1,0.3,1.0 mg/kg(intravenous, i.v.),2.0?g(intracerebroventricular,i.c.v.)and 1.0,10.0 mg/kg(intragastric,i.g.)were administrated in different groups of rats.To evaluate the roles of?_1-adrenoceptors,?_2-adrenoceptors and I_1-imidazoline receptors in the transient pressor responses to moxonidine,prazosin(10.0?g/kg),yohimbine(2.0 mg/kg),phentolamine(0.2 mg/kg),idazoxan(1.0 mg/kg) or yohimbine+idazoxan(2.0 mg/kg+1.0 mg/kg)were intravenously given to the animals before moxonidine 0.3 mg/kg (i.v.).Results:It was found that i.v.moxonidine produced a greater pressor response than clonidine when producing a similar reduction of blood pressure.This effect of moxonidine was not influenced by prazosin,but was partly inhibited by yohimbine, phentolamine or idazoxan,and completely blocked by the combination of yohimbine and idzaxon.Neither i.c.v.injection nor i.g.administration of moxonidine induced transient pressor responses.Conclusion:The transient pressor response of i.v.mox- onidine is mediated by both peripheral I_1-imidazoline receptors and?_2-adrenoceptors.
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Objective To investigate the changes of uveoscleral pathway by an I1 receptor agonist,moxonidine,and with pretreatment of antagonists topical administration,and to study the mechanism that moxonidine improves uveoscleral outflow.Methods Moxonidine was administered unilaterally and topically to rabbits and with pretreatment of the antagonists,namely,prazosin,yohimbine and efaroxan.FITC-BSA,a tracer agent,was injected into the anterior chamber after moxonidine treatment or with pretreatment of the antagonists.Frozen sections were undertaken at different time points between 2 to 10 h.Fluorescence intensity was observed in the sites of uveoscleral pathway in the sections by fluorescence microscopy.Results Bilateral fluorescence intensity treated with moxonidine was more intense than that with placebo,and the most intense regions of fluorescence were ciliary body and superchoroidal space.Fluorescence intensity by prazosin pretreatment was not significantly different compared to that by moxonidine,while yohimbine and efaroxan pretreatment decreased the intensity compared with moxonidine(P
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Objective To study the effect of moxonidine (Mox) on the His bundle electrogram (HBE) of normal rabbits. Methods A total of 24 healthy rabbits were randomly divided into four groups: control group, small dose of Mox (0.1 mg?kg -1), medium dose of Mox (0.3 mg?kg -1) and large dose of Mox (0.9 mg?kg -1). The electrode catheter was inserted from the right carotid artery to record the HBE. The HBE and the synchronism surface ECG were recorded before and after intravenous injection. Results In normal rabbits, the R-R interphase, P-R interphase of the ECG and the H-V interphase of the HBE were prolonged in a dose-dependent manner after intravenous injection of Mox. Mox exerted no significant influence on the A-H interphase. Conclusion ① Mox decreases the heart rate of rabbits in a dose-dependent manner in vivo. ② Mox dose-dependently prolongs the P-R interphase of the surface ECG and the H-V interphase of HBE. This indicates that Mox mainly acts on the intraventricular conducting system.