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

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Myocardial beta-adrenoceptor down-regulation by norepinephrine is linked to reduced norepinephrine uptake activity.
    Author: Dong E, Yatani A, Mohan A, Liang CS.
    Journal: Eur J Pharmacol; 1999 Nov 12; 384(1):17-24. PubMed ID: 10611414.
    Abstract:
    Chronic administration of norepinephrine for 8 weeks has been shown to reduce neuronal norepinephrine uptake activity and increase interstitial norepinephrine concentration in the heart. To determine whether the changes could lead to myocardial beta-adrenoceptor down-regulation or beta-adrenergic subsensitivity, we measured left ventricular contractile responses to dobutamine, myocardial beta-adrenoceptor density, beta subtype distribution, competitive inhibition agonist binding, and adenylyl cyclase activity activation by isoproterenol, 5'-guanylylimidodiphosphate, and forskolin in dogs after a norepinephrine or saline infusion for 8 weeks. We found that norepinephrine infusion reduced myocardial beta-adrenoceptor density, beta(1)-adrenoceptor subtype density, and high-affinity site for isoproterenol. Left ventricular contractile responses to dobutamine were reduced in the norepinephrine-infused animals. In addition, norepinephrine infusion decreased the basal adenylyl cyclase activity and the adenylyl cyclase responses to isoproterenol, 5'-guanylylimidodiphosphate, and forskolin. The findings indicate that a decrease in cardiac norepinephrine uptake predisposes the heart to norepinephrine-induced myocardial beta-adrenoceptor down-regulation, and that norepinephrine, when present in a sufficient amount over a long period as it is in chronic heart failure, can reduce myocardial beta-adrenergic responsiveness by both homologous and heterologous desensitization.
    [Abstract] [Full Text] [Related] [New Search]