• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.115-122
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• 1986

To delineate the relationship between subtypes of central alpha-adrenoceptor and central calcium channel, influences of intracerebroventricular (icv) diltiazem and nifedipine on the changes of blood pressure and heart rate by icv methoxamine and clonidine were investigated in urethane-anesthetized rabbits. 1) Methoxamine (1mg, icv) produced pressor and bradycardiac effect and clonidine $(30\;{\mu}g,\;icv)$ produced hypotension and bradycardia. 2) Icv diltiazem and nifedipine elicited dose-dependent deprcssor and bradycardiac responses. The depressor response to nifedipine was more prominent than that to diltiazem but the bradycardiac effect of nifedipine was smaller than that of diltiazem. The depressor responses to icy nifedipine $(35{\mu}g)$ and icv diltiazem $(400{\mu}g)$ were persistent but those to intravenous (iv) nifedipine $(35{\mu}g/kg)$ and diltiazem $(200{\mu}g/kg)$ were transient. 3) The pressor response to methoxamine was little affected by pretreatment with in diltiazem $(400{\mu}g)$ or icv nifedipine $(35,\;350{\mu}g)$ but the bradycardiac response to methoxamine was significantly attenuated by the same pretreatment. 4) The depressor response to clonidine was markedly attenuated by pretreatment with icv diltiazem $(400{\mu}g)$ or icv nifedipine $(35,\;350{\mu}g)$ but not affected by pretreatment with iv diltiazem $(200{\mu}g/kg)$ or iv nifedipine $(20{\mu}g/kg)$. Pretreatment with icv and iv diltiazem or nifedipine reduced the bradycardiac effect of clonidine. 5) Pretreatment with icv clonidine had no effect on the depressor and bradycardiac responses to in diltiazcm or icv nifedipine. These results indicate that diltiazem and nifedipine have no effect on icv methoxamine-induced pressor response elicited by the activation of central alpha-l adrenoceptors whereas the icv clonidine-induccd depressor and bradycardiac effects which result from the activation of central alpha-2 adrenoceptors are inhibited by the calcium antagonists.

• Korean Journal of Veterinary Research
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• v.39 no.4
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• pp.710-714
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• 1999

In veterinary medicine amitraz has been used as an insecticide to eliminate mites, lice, and ticks in dogs, cats, goats, swine and cattle. We performed the experiment on bradycardiac effect of arnitraz in rabbits. Under anesthetized with urethane (1g/kg, 25% w/v, SC), the femoral artery was cannulated by a polyvinyl tube which was connected with pressure transducer for continuous measurement of heart rate. Amitraz (0.5-2.5mg/kg, IV) reduced the heart rate in a dose-dependent manner. Pretreatment of yohimbine (2.0mg/kg) or atropine (2.0mg/kg and 4.0mg/kg) affected the response of amitraz but pretreatment of prazosin (0.5mg/kg) or propranolol (1.0mg/kg) did not. Moreover, the effect of amitraz was blocked by vagotomy. The result of our experiment suggest that amitraz may reduce the heart rate by increasing acetylcholine through activating vagal nerves and ${\alpha}_2$-adrenoceptors could be involved in activating vagal nerves.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.205-207
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• 1996

Clonidine, an antihypertensive drug, stimulates postsynaptic alpha-2 adrenergic receptors in the central nervous system and lowers arterial pressure through the effects on both cardiac output and peripheral resistance. However, many patients experience that sedation and xerostomia occur upon oral administration of clonidine. These side effects are due to high plasma peak concentration and can be avoided when clonidine is given transdermally. In this study, we tested the antihypertensive effects of trandermal administration of clonidine patch on spontaneously hypertensive rat (SHR) which is a model animal for human essential hypertension. Forty eight SHR (male) were divided into six groups according to the dose levels, respectively. After transdermal administration of clonidine patch of each dose, systolic blood pressure and heart rate were measured. Clonidine patch produced maximal antihypertensive and bradycardiac effects 48 hrs after administration and antihypertensive effects showed dose-dependency. We suggest that antihypertensive effects of clonidine patch are similar to those of orally given clonidine and clonidine patch can be used instead of clonidine tablet.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.313-319
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• 1994

This study was undertaken to investigate the relationship between the $Na^+$ channels of the cardiovascular regulation center and the responses to increased $Na^+$ concentration in the cerebrospinal fluid (CSF), by observing the effects of icv administration of the agents affecting $Na^+$ transport. Icv infusion of $200\;{\mu}l$ of 1 M NaCl produced hypertension and bradycardia in the urethane-anesthetized rabbit, and the bradycardia was inhibited and reversed to tachycardia by vagotomy. Amiloride, a $Na^+$ transport inhibitor, produced hypertension and bradycardia, which were not altered by vagotomy, and it did not affect the NaCl-induced responses. Benzamil, a derivative of amiloride with higher specificity, neither produced any cardiovascular effects by itself, nor affected the NaCl-induced responses. In vagotomized rabbits, icv amiloride reversed the NaCl-induced tachycardia to a bradycardia, but the bradycardiac effect was not altered by pretreating with NaCl. This study showed that although amiloride and benzamil slightly differ in their cardiovascular action, neither of them did affect the NaCl-induced responses. We suggest that the $Na^+$ channels which are sensitive to amiloride or benzamil in the cardiovascular regulation center are not involved in the NaCl-induced response.