DIFFERENTIAL CARDIOVASCULAR EFFECTS OF 8-HYDROXY-2-(DI-N-PROPYLAMINO) TETRALIN (8-OH-DPAT), FLESINOXAN, 5-METHYL-URAPIDIL AND MDL-75,608A IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS

被引:4
作者
BUISSONDEFFERIER, S [1 ]
HIBERT, M [1 ]
VANDENBUUSE, M [1 ]
机构
[1] MARION MERRELL DOW,RES INST,STRASBOURG RES CTR,F-67046 STRASBOURG,FRANCE
关键词
SEROTONIN; 5-HT(1A)-RECEPTOR; BLOOD PRESSURE; HEART RATE; SPONTANEOUSLY HYPERTENSIVE RAT; DESENSITIZATION; ALPHA(1)-ADRENOCEPTOR;
D O I
10.1111/j.1472-8206.1993.tb00254.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of intravenous (iv) administration of four agonists at central 5-HT1A receptors were investigated and compared Acute iv injection of 0.1 mg/kg of 8-OH-DPAT induced a decrease in blood pressure both in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The maximal hypotensive effect was observed 15 and 10 min after injection, respectively, but the effect was greater and longer-lasting in the SHR. 8-OH-DPAT significantly decreased heart rate in WKY and, to a lesser extent, in SHR. The iv injection of 1 mg/kg of flesinoxan caused a similar fall in blood pressure and heart rate in SHR and WKY. The iv administration of 1 mg/kg of 5-methyl-urapidil or MDL 75,608A caused a fall in blood pressure which was significantly more pronounced in HR than in WKY. 5-methyl-urapidil induced a significant tachycardia in WKY, but had little effect on heart rate in SHR. MDL 75,608A caused a short-lasting tachycardia in SHR and WKY. In conscious SHR, the intracerebroventricular (icv) injection of 10 mug of 8-OH-DPAT or 100 mug of either flesinoxan or MDL 75,608A caused a decrease in blood pressure and heart rate. The icv injection of 100 mug of 5-methyl-urapidil caused only a decrease in blood pressure. Chronic pre-treatment with these compounds, by daily iv injection, did not significantly influence the hypotensive or bradycardic effects in an acute experiment. The involvement of alpha1-adrenoceptors in the effects of these compounds was studied by administering phenylephrine (1 mug/iv) at 5- min intervals before and after the iv injection of the experimental compounds. The injection of phenylephrine reproducibly increased blood pressure by 3540 mm Hg after saline pre-treatment, and these responses were not affected by the iv injection of 0.1 mg/kg of either 8-OH-DPAT or 1 mg/kg of flesinoxan. In contrast, the phenylephrine-induced pressor responses were markedly diminished at 5 min after treatment with 1 mg/kg of either 5-methyl-urapidil or MDL 75,608A, but slowly recovered thereafter. These results show that the 5-HT1A receptor agonists 8-OH-DPAT, flesinoxan, 5-methyl-urapidil and MDL 75,608A show antihypertensive properties in conscious SHR after iv or icv injection. However, the mechanism of action of the compounds differs: 8-OH-DPAT and flesinoxan may act predominantly as 5-HT1A receptor agonists, where as 5-methyl-urapidil and MDL 75,608A also seem to have an effect on peripheral alpha1-adrenoceptors.
引用
收藏
页码:499 / 511
页数:13
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