Endogenous opioid dependence--a basic pathophysiological phenomenon of stress-induced and genetically fixed disturbances in adaptation--influence of substance P.
Disturbances in adaptive processes can be induced by chronic exposition to stress or can result from a genetical predisposition. Experimental data of chronically stressed Wistar rats and of spontaneously hypertensive rats (SHR) demonstrate a relation between a decreased level of substance P (SP) in adrenals, the existence of a dependence on endogenous opioid peptides and an increased regulatory level of blood pressure. The endogenous level of SP was determined by using a RIA. The dependence (physical) on endogenous opioid peptides was detected by using the method of "gut dependence". SP injection i.p. once a day for 4 d antagonized the dependence on endogenous opioid peptides and normalized the increased level of blood pressure in both animal models. Investigations on SHR had shown that the adaptive effect of SP on blood pressure and endogenous opioid dependence is bound to the premise of an acute stimulated endogenous opioid system at the moment of SP-application. Experimental findings suggest that different systems of opioid peptides take part in the etiopathogenesis of genetically predisposed hypertension of SHR and in stress-induced increase of blood pressure level of Wistar rats. The effect of SP on blood pressure and endogenous opioid dependence will be discussed as a result of the modulatory influence on the cholinergic-opioid-peptidergic interaction.
Roske
I
I
Institute of Drug Research, Berlin.
Nieber
K
K
Oehme
P
P
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004723:Endorphins / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology; D007082:Ileum / Q000187:drug effects; D007103:Immobilization; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013315:Stress, Psychological / Q000503:physiopathology*; D013373:Substance P / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000503:physiopathology*
D004723:Endorphins; D013373:Substance P