An endomorphine analog ([d-Ala(2)]-Endomorphin 2, TAPP) lowers blood pressure and enhances tissue nitric oxide in anesthetized rats.

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.