Naloxone's effect on the inotropic and chronotropic responses of isolated, electrically stimulated or spontaneously beating rat atria

Abstract

Experiments were conducted to determine (i) how naloxone administration alone could modify the inotropic (in electrically stimulated (ES) rat atria) and both the inotropic and chronotropic responses (in spontaneously beating (SB) rat atria) isolated from normotensive and hypotensive (hemorrhaged) rats, and (ii) how naloxone administration would modify the inotropic and chronotropic responses of isolated rat atria previously administered an opiate agonist (morphine), a muscarinic agonist (carbachol), or an α - and β-adrenergic agonist (noradrenaline). Naloxone (51–340 μM) added to ES atria caused a delayed but dose-related decrease in atrial tension (AT), whereas in SB atria, naloxone caused atrial heart rate (AHR) to fall and atrial tension (AT) to increase. Naloxone (68–340 μM), given to SB atria from acutely hypotensive rats, caused a similar increase in atrial tension as seen in the "normotensive" isolated (SB) atria and a similar decrease in atrial heart rate. Morphine sulphate (MS), 37–375 μM, administered to ES atria caused a delayed fall in AT, which was further decreased when naloxone (340 μM) was also added. In the SB atria, morphine caused a dose-related decrease in atrial heart rate whereas atrial tension increased. In SB preparations, atrial heart rate fell even further when naloxone was added to morphine compared with when morphine sulphate was given alone, whereas atrial tension was increased. Noradrenaline (3 or 12 μM) caused a positive, dose-related inotropic response in the ES atria, effects not influenced by the addition of naloxone. In the SB atria, naloxone caused no change in the dose-related increases in atrial tension and heart rate when combined with the lower dose of noradrenaline but decreased AT when combined with 12 μM noradrenaline, compared with when this dose of noradrenaline was given alone. Carbachol (683 nM – 1.37 μM) caused a dose-related decrease in atrial tension in ES atria, which was reversed completely by the addition of naloxone. In SB atria, carbachol decreased both atrial tension and heart rate, and with the addition of naloxone (340 μM), a further slight drop in atrial heart rate occurred, but concurrently, a marked rise in atrial tension was observed. The results indicate that naloxone can act with receptors directly within atrial tissue to cause changes in atrial tension and heart rate. The comparable delayed responses of morphine and naloxone suggest their effects are mediated by nonopiate receptors which, in time, cause decreases in calcium influx into the atria. The marked rise in atrial tension following naloxone administration in atria previously given carbachol suggest there is an interaction between naloxone- and carbachol-sensitive receptors in the atria. The net result of this interaction may again reflect a change (increase) in calcium influx into myocardial cells.Key words: rat atria, inotropy, chronotropy, morphine, carbachol, noradrenaline, acute hypotension.