title: An endomorphine analog ([d-Ala(2)]-Endomorphin 2, TAPP) lowers blood pressure and enhances tissue nitric oxide in anesthetized rats.
abstract: BACKGROUND
  Activation of opioid receptors can alter cardiovascular function, an action possibly mediated by nitric oxide (NO). In this study we examined the effects of ([d-Ala(2)]-Endomorphin 2, TAPP), a synthetic opioid μ-receptor agonist, on blood pressure (MABP), tissue NO bioavailability and renal hemodynamics and excretion.
  
  
  METHODS
  In acute experiments with anesthetized normotensive male Sprague-Dawley rats TAPP was given as a short iv infusion at a dose of 1.2 or 12mg/kg and then MABP, renal medullary NO signal (polarographic electrode), total renal blood flow (RBF, renal artery Transonic probe), renal regional perfusion (laser-Doppler fluxes) and renal excretion were simultaneously measured over 2h.
  
  
  RESULTS
  After 1.2mg/kg dose MABP decreased progressively from 121±7 to 114±9mmHg (-6%, p<0.05) while kidney tissue NO signal increased from 29.1±2.7 to 31.7±3.1nA (6%, p<0.04). Both effects were prevented by Naloxone methiodide, a peripheral opioid receptor inhibitor. RBF and renal regional perfusion were not altered by either dose of TAPP; renal sodium excretion changes were highly variable and were not affected by Naloxone pretreatment.
  
  
  CONCLUSIONS
  Briefly, we found that in anesthetized normotensive rats stimulation of peripheral opioid receptors with TAPP caused a prolonged decrease in arterial pressure, a change that was associated and probably causally related to an increase in tissue NO. The data suggest that synthetic opioids that do not penetrate the blood-brain barrier and are potentially non-addictive could be considered for antihypertensive therapy.
authors.affiliation: Department of Renal and Body Fluid Physiology, Polish Academy of Sciences, Warszawa, Poland. Electronic address: martakuczeriszka@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Kuczeriszka
authors.affiliation: Department of Neuropeptides Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
authors.affiliation: Department of Renal and Body Fluid Physiology, Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Sadowski
authors.affiliation: Department of Renal and Body Fluid Physiology, Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kompanowska-Jezierska
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine
chemical_list: C000620772:((D-Ala(2))-endomorphin 2; D009842:Oligopeptides; D000644:Quaternary Ammonium Compounds; D009569:Nitric Oxide; D009270:Naloxone; C041269:N-methylnaloxone; D012964:Sodium
keywords: Arterial blood pressure; Renal hemodynamics; Synthetic opioid receptor agonist; Tissue nitric oxide