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Pressor Responses to Ephedrine Are Mediated by a Direct Mechanism in the Rat

2005; American Society for Pharmacology and Experimental Therapeutics; Volume: 316; Issue: 1 Linguagem: Inglês

10.1124/jpet.105.090035

1521-0103

John T. Liles, Paul A. Dabisch, Keith E. Hude, Leena Pradhan, Kurt J. Varner, Johnny R. Porter, Alissa R. Hicks, Conni Corll, Syed R. Baber, Philip J. Kadowitz,

Hormonal and reproductive studies

The mechanism of the pressor response to ephedrine is controversial. In the present study. i.v. injections of ephedrine increased systemic and pulmonary arterial pressure, and i.a. injections decreased hindlimb blood flow in a dose-related manner. Responses to ephedrine were inhibited by α-receptor blocking agents and were not attenuated by blockade of the norepinephrine reuptake transporter (NET) or by catecholamine depletion using reserpine or a combination of reserpine and α-methyl-p-tyrosine, whereas responses to tyramine and amphetamine were inhibited by these treatments. The magnitude of the pressor response to ephedrine was similar in anesthetized and conscious rats. Tachyphylaxis developed to pressor responses to ephedrine and amphetamine with sequential injections; however, ephedrine tachyphylaxis differed in that subsequent responses to α-receptor agonists were attenuated. These results suggest that the systemic and pulmonary pressor and hindlimb vasoconstrictor responses to ephedrine are mediated by direct action on α-adrenergic receptors and that the release of norepinephrine from adrenergic terminals plays no significant role. These results provide support for the hypothesis that responses to ephedrine are directly mediated in the intact rat, whereas responses to amphetamine are mediated in a large part by the release of norepinephrine from adrenergic terminals.