Physiologic role of the peripheral enkephalinergic system in regulating cardiovascular homeostasis: evidence of interactions with the renin-angiotensin and kallikrein-kinin systems.
On isolated heart preparation, it was found that Leu5-Enkephalin (Leu5-ENK) did not influence the cardiac function. On the other hand, Leu5-ENK induced a specific dose-related inhibition, in the cardiac perfusate, of the activities of kininase II (KII) and angiotensin converting enzyme (ACE) (but not of kininase I-KI). Instead no detectable alterations of the above enzymatic activities with the used concentrations of Leu5-ENK were observed in vitro. This opioid also increased specifically the effects induced by some of the autacoids, related to both renin-angiotensin and kallikrein-kinin systems, on the KII and ACE activities. A specific correlation between these Leu5-ENK-induced modifications and the functional responses of the heart to the same autacoids was observed. Naloxone (NAL) and more significantly ICI 174864 (ICI) opposed or reversed the inhibitory effect of the used opioid whereas they had neither inhibitory nor synergic effect on both KII and ACE activity by themselves. The possible physiologic role of the enkephalins in regulating cardiovascular function by acting peripherally on some humoral systems through modulatory mechanism was discussed.
Carmignani
M
M
Dept. of Pharmacology, Catholic University, School of Medicine, Rome, Italy.
Porcelli
G
G
Volpe
A R
AR
Preziosi
P
P
D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism*; D002320:Cardiovascular Physiological Phenomena; D003326:Coronary Circulation / Q000187:drug effects*; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D004745:Enkephalins / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D006706:Homeostasis; D066298:In Vitro Techniques; D007610:Kallikreins / Q000502:physiology*; D007705:Kinins / Q000494:pharmacology / Q000502:physiology*; D001121:Lysine Carboxypeptidase / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000502:physiology*
D004745:Enkephalins; D007705:Kinins; D004743:Enkephalin, Leucine; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D007610:Kallikreins