Intrathecal administration of delta receptor agonists in the urethane anesthetized rat provokes an increase in arterial pressure via a non-opioid mechanism.
Intrathecal administration of the delta receptor specific agonists Leu5-enkephalin (Leu-Enk; 300 nmol), Met5-enkephalin (Met-Enk; 300 nmol) and [D-Pen2,D-Pen5]enkephalin (DPDPE; 100 nmol) to the T2 or the T9 segment of the rat spinal cord provoked a transient (less than 5 min) increase (15-20 mm Hg) in arterial pressure. DPDPE, but not Leu-Enk or Met-Enk, also significantly increased heart rate by 30-35 bpm. Intravenous administration of 300 nmol of Leu-Enk mimicked the effects observed following intrathecal administration. The hypertensive effect of intrathecal and intravenous Leu-Enk administration was blocked by prior systemic administration (10 mg/kg) of the nicotinic ganglion blocker hexamethonium, suggesting that the effect was mediated via sympathetic activation. The increase in arterial pressure observed following intrathecal Leu-Enk administration was not blocked by either intrathecal (305 nmol) or intravenous (10 mg/kg) administration of the opiate receptor blocker naloxone, although naloxone did block the hypertension provoked by intravenous Leu-Enk administration. Moreover, intrathecal administration of Des-Tyr1-Leu-Enk (300 nmol), an enkephalin fragment devoid of opiate receptor activity, also increased arterial pressure. These results suggest that the hypertension elicited by intrathecal delta agonist administration was not mediated via an opioid mechanism.
Rochford
J
J
Department of Physiology, McGill University, Montreal, Que., Canada.
Henry
J L
JL
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D014520:Urethane
D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D009270:Naloxone; D014520:Urethane; D004743:Enkephalin, Leucine; C042087:enkephalin-Leu, des-Tyr(1)-; D020881:Enkephalin, D-Penicillamine (2,5)-