The cardiovascular and renal effects of the potent and highly selective mu opioid agonist [Dmt1]DALDA.
The cardiovascular and renal effects of a mu opioid agonist, [Dmt]DALDA, were studied in conscious Sprague-Dawley rats. During the first hour postinjection, [Dmt]DALDA (0.025-250 microg/rat, IV) evoked a dose-dependent diuresis. The dose of 2.5 microg increased urine volume from 1.0 +/- 0.2 to 3.4 +/- 0.3 mL/h (P < 0.001, n = 30), urinary excretion of sodium, potassium, and cGMP, and induced a mild antihypertensive effect. This dose increased cumulative 4-hour urine volume but significantly inhibited sodium and potassium excretions. The renal and cardiovascular effects were abolished by naloxone (4 mg/kg), but not by naloxonazine (35 mg/kg SC), a selective mu-1 receptor antagonist. Pretreatment with 8 mg/kg naloxone methiodide, an opioid antagonist with limited access to the brain, partially inhibited the renal effects of [Dmt]DALDA. Inhibition of nitric oxide synthases with L-NAME (1 mg/kg) had no effect on the renal and cardiovascular actions of [Dmt]DALDA. Plasma ANP and AVP, measured at 20 and 120 minutes after injection, were not altered by 2.5 and 25 microg [Dmt]DALDA. Therefore, [Dmt]DALDA evokes renal and cardiovascular effects that may primarily be mediated by central naloxonazine-insensitive mu opioid receptors (non-mu-1). These findings indicate that the central mu opioid system is involved in the regulatory mechanism of renal handling of sodium and water.
Gutkowska
J
J
Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de l'Université de Montréal-Hô-Dieu, Université de Montréal, Montréal, Québec, Canada. jolanta.gutkowska@umontreal.ca
Mukaddam-Daher
S
S
Jankowski
M
M
Schiller
P W
PW
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*; D014667:Vasopressins / Q000502:physiology
C424424:2',6'-dimethyltyrosyl-arginyl-phenylalanyl-lysinamide; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D000644:Quaternary Ammonium Compounds; D017450:Receptors, Opioid, mu; D014667:Vasopressins; D009569:Nitric Oxide; D009270:Naloxone; C041269:N-methylnaloxone; C034643:naloxonazine; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester