Comparison of cardiovascular and bronchoconstrictor effects of substance P, substance K and other tachykinins

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Abstract
The effects of substance P (SP), substance K (SK), physalaemin, eledoisin, kassinin, neuromedin K and bombesin on blood pressure, heart rate, respiratory insufflation pressure and plasma extravasation were studied in the guinea-pig. All tachykinins except neuromedin K caused a fall in blood pressure with rather similar potency. The hypotensive response after physalaemin was comparatively more long-lasting. SK and eledoisin (2.5 nmol×kg−1 i.v.) caused an initial bradycardia which then changed into tachycardia. The other tachykinins induced a slowly developing tachycardia. Neuromedin K (up to 40 nmol×kg−1) did not influence heart rate. SK, kassinin and eledoisin were more potent than SP and physalaemin in increasing respiratory insufflation pressure. The effect of SK had a particularly long duration. Neuromedin K only induced a weak increase in insufflation pressure at a very high dose. All tachykinins except neuromedin K induced an increase in vascular permeability to plasma proteins in many visceral organs, as indicated by Evans blue extravasation. The trachea and ureter were the most sensitive organs with regard to this effect. Physalaemin and eledoisin were generally more potent in increasing vascular permeability in various organs than SP and SK. The maximal permeability-increasing effect of SK was smaller than that of SP, although the potency was similar. Bombesin increased insufflation pressure with no clearcut effects on vascular permeability. It is concluded that in the same species, i.e. guinea-pig, several tachykinins have rather similar hypotensive action, while the vascular permeability increase to plasma proteins is especially pronounced after physalaemin and eledoisin. SK, kassinin and eledoisin have prominent bronchoconstrictor effects. Neuromedin K, however, displays poor activity in the present models. The existence of novel tachykinins such as SK in addition to SP in mammalian tissues suggests that effects seen upon antidromic stimulation of sensory nerves may be caused by several structurally related peptides.