Glycyl-L-glutamine [beta-endorphin-(30-31)] attenuates hemorrhagic hypotension in conscious rats.
The profound hypotension caused by acute hemorrhage is thought to involve opioid peptide neurons. In this study, we tested whether glycyl-L-glutamine [Gly-Gln; beta-endorphin-(30-31)], a nonopioid peptide derived from beta-endorphin processing, prevents the cardiovascular depression induced by hemorrhage in conscious and anesthetized rats. Previously, we found that Gly-Gln inhibits the hypotension and respiratory depression produced by beta-endorphin and morphine but does not affect opioid antinociception. Hemorrhage (2.5 ml/100 g body wt over 20 min) lowered arterial pressure in conscious rats (from 120.1 +/- 2.9 to 56.2 +/- 4.7 mmHg) but did not change heart rate significantly. Intracerebroventricular Gly-Gln (3, 10, or 30 nmol) pretreatment inhibited the fall in arterial pressure and increased heart rate significantly. The response was dose related and was sustained during the 35-min posthemorrhage interval. Pentobarbital sodium anesthesia potentiated the hemodynamic response to hemorrhage and attenuated the effect of Gly-Gln. Gly-Gln (10 or 100 nmol icv) did not influence arterial pressure or heart rate in normotensive rats. These data indicate that Gly-Gln is an effective antagonist of hemorrhagic hypotension.
Owen
M D
MD
Department of Anesthesia, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
Gürün
S
S
Zaloga
G P
GP
Millington
W R
WR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000150:complications / Q000503:physiopathology*; D007022:Hypotension / Q000503:physiopathology / Q000517:prevention & control*; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009433:Neural Inhibition; D011674:Pulse; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D004151:Dipeptides; C039788:glycylglutamine; D009270:Naloxone