Antagonism by (D‐Pro2, D‐Trp7,9)‐substance P of the cerebrovascular dilatation induced by substance P

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Abstract
The effects of (D‐Pro2, D‐Trp7,9)‐substance P, a structural analogue of substance P, were examined in two models on cerebrovascular responses to substance P (SP) in cats; in vitro using segments of the middle cerebral artery and in situ by microapplication of the peptides close to pial arterioles. (D‐Pro2, D‐Trp7,9)‐SP in concentrations up to 6.6×10‐6 M was without significant effect upon isolated middle cerebral arteries under normal conditions and in arteries contracted with prostaglandin F2a. SP caused concentration‐dependent relaxations of middle cerebral arteries contracted by prostaglandin F2a (mean ± SE; EC50: 2.0±1.6×10‐9 M). The presence of (D‐Pro2, D‐Trp7,9)‐SP shifted the concentration‐response curve of SP towards higher concentrations without significantly effecting the maximum response of the arteries to SP. A relaxation by 24.2±4.0% (n=6) was obtained in prostaglandin F2a contracted arteries by increasing the potassium concentration with 2 mM in the buffer solution. This response to potassium was unaltered in the presence of 6.6×10‐6 M of (D‐Pro2, D‐Trp7,9)‐SP (25.0±7.1%, n=5). Perivascular microapplication of SP around individual pial arterioles in situ effected dose‐dependent increases in vascular calibre (mean response 14.5±2% with SP, 10‐7 M). The concomitant perivascular administration of (D‐Pro2, D‐Trp7,9)‐SP (6.6×10‐6 M), which alone did not alter the arteriolar calibre, attenuated significantly the cerebrovascular response to SP (mean response 1.5±3.2%). On the basis of the agonist‐antagonist relation found, these observations point to the possibility of a specific SP receptor site in cerebral arteries and arterioles.