These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


PUBMED FOR HANDHELDS

Search MEDLINE/PubMed


  • Title: 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.
    Author: Buisson-Defferier S, Hibert M, van den Buuse M.
    Journal: Fundam Clin Pharmacol; 1993; 7(9):499-511. PubMed ID: 7906241.
    Abstract:
    The effects of intravenous (i.v.) 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 i.v. injection of 1 mg/kg of flesinoxan caused a similar fall in blood pressure and heart rate in SHR and WKY. The i.v. 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 SHR 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 micrograms of 8-OH-DPAT or 100 micrograms of either flesinoxan or MDL 75,608A caused a decrease in blood pressure and heart rate. The icv injection of 100 micrograms of 5-methyl-urapidil caused only a decrease in blood pressure. Chronic pre-treatment with these compounds, by daily i.v. injection, did not significantly influence the hypotensive or bradycardic effects in an acute experiment. The involvement of alpha 1-adrenoceptors in the effects of these compounds was studied by administering phenylephrine (1 microgram/i.v.) at 5-min intervals before and after the i.v. injection of the experimental compounds. The injection of phenylephrine reproducibly increased blood pressure by 35-40 mm Hg after saline pre-treatment, and these responses were not affected by the i.v. 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 alpha 1-adrenoceptors.
    [Abstract] [Full Text] [Related] [New Search]