Action of substance P and an analogue on blood pressure and avoidance learning in rats with spontaneous hypertension (SHR).

Substance P (SP) and an analogue (Lys-Phe-Ile-Gly-Leu-MetNH2 = EH) were tested in acute experiments on the blood pressure in the intact rat anaesthetized with urethane. A biphasic response, consisting of an initial depressor, followed by a pressor component, was seen. In low concentrations, SP decreases blood pressure, in medium concentrations SP produces a pronounced biphasic response, in high concentrations SP produces only hypertensive reactions. In chronic experiments, SP-peptides act also in different directions. After EH, disorders in avoidance learning were completely eliminated from 10 weeks old spontaneously hypertensive rats (SHR) or conditionally from SHR age 14 or 26 weeks. Elevated blood pressure in SHR aged 26 weeks was reduced by EH. Blood pressure in SHR aged 14 weeks was almost unaffected by EH and blood pressure went up in ten weeks old SHR. SP had a weaker action in comparison with EH. These results are in agreement with the hypothesis proposed by Oehme and co-workers [11-13] that SP can act as a regulatory peptide (="regulide").