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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/H967    most recent 00909.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bolte, C. Articles by Schultz, J. E. J. Search for Related Content PubMed PubMed Citation Articles by Bolte, C. Articles by Schultz, J. E. J.

Hypertensive state, independent of hypertrophy, exhibits an attenuated decrease in systolic function on cardiac -opioid receptor stimulation

Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio

Submitted 18 August 2008 ; accepted in final form 26 January 2009

Opioids/opiates are commonly administered to alleviate pain, unload the heart, or decrease breathlessness in patients with advanced heart failure. As such, it is important to evaluate whether the myocardial opioidergic system is altered in cardiac disease. A hamster model of spontaneous hypertension was investigated before the development of hypertension (1 mo of age) and in the hypertensive state (10 mo of age) to evaluate the effect of prolonged hypertension on myocardial opioidergic activity. Plasma β-endorphin was decreased before the development of hypertension and in the hypertensive state (P < 0.05). There was no change in cardiac β-endorphin content at either time point. No differences were detected in cardiac or plasma dynorphin A, Met-enkephalin, or Leu-enkephalin, or in cardiac peptide expression of - or -opioid receptors. µ-Opioid receptor was not detected in either model. To determine how hypertension affects myocardial opioid signaling, the ex vivo work-performing heart was used to assess the cardiac response to opioid administration in healthy hearts and those subjected to chronic hypertension. Agonists selective for the - and -opioid receptors, but not µ-opioid receptors, induced a concentration-dependent decrease in cardiac function. The decrease in left ventricular systolic pressure on administration of the -opioid receptor-selective agonist, U50488H, was attenuated in hearts from hamsters subjected to chronic, untreated hypertension (P < 0.05) compared with control. These results show that peripheral and myocardial opioid expression and signaling are altered in hypertension.

hypertension; hamsters; cardiac physiology; cardiac function; β-endorphin; cardiac opioid receptors