Blood pressure responses of conscious rats to intravenous administration of enkephalin derivatives (D-ala2 methionine and leucine enkephalinamide, and methionine and leucine enkephalinamide.
The present study was designed to determine the blood pressure (BP) responses of conscious rats given intravenous (IV) injections of enkephalin derivatives (D-ala2-methionine enkephalinamide, DAMEA; D-ala2-leucine enkephalinamide, DALEA; methionine enkephalinamide, MEA; leucine enkephalinamide, LEA) and the receptor mechanisms mediating the resultant change in BP. IV injection of 1.6-16.0 nmoles of DAMEA or DALEA caused a transient but potent decrease in mean arterial pressure (MAP) and mean heart rate (MHR). LEA and MEA (16.0 nmoles) given IV produced slight pressor responses, which were not associated with concomitant tachycardia whereas 48 nmoles of MEA elicited a hypotensive effect accompanied by a fall in MHR. Pretreatment studies whereby various receptor antagonists (naloxone, diprenorphine, phentolamine, D-L-propranolol or atropine) were given IV 5 min before subsequent IV administration of DAMEA, DALEA, MEA or LEA (16 nmoles) showed that naloxone, diprenorphine and atropine blocked the depressor and bradycardic effects of DALEA and DAMEA. Naloxone and phentolamine suppressed the pressor response of both MEA and LEA (16.0 nmoles) while diprenorphine blocked the rise in MAP to only MEA. The results show that DAMEA and DALEA mediate their depressor actions in conscious rats via a negative chronotropic effect through an interaction of muscarinic cholinergic receptors on the myocardium. It suggested that the pressor response of MEA and LEA may be produced via an alpha-receptor mediated effect on the peripheral vasculature to cause vasoconstriction.
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003243:Consciousness; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; C021055:Met-enkephalinamide; C048614:enkephalinamide-Leu; C013801:enkephalin-Met, Ala(2)-; D016308:Enkephalin, Leucine-2-Alanine; C030279:enkephalinamide-Leu, Ala(2)-