EFFECT OF SUBSTANCE P AND OTHER TACHYKININS ON ARTERIAL PRESSURE IN GUINEA‐PIGS

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Abstract
The blood pressure and respiratory effects of i.v. administration of the tachykinins substance P (SP), physalaemin (P), eledoisin (E) and kassinin (K) and purported antagonists of SP were compared in guinea-pigs anesthetized with sodium pentobarbital. Tachykinins caused a dose-dependent decrease in diastolic and systolic pressure with systolic pressure decreased more than diastolic. Heart rate was not affected. Duration of response was directly related to dosage. These data are in agreement with observations that tachykinins decrease peripheral vascular resistance in other species. Tachyphylaxis did not develop to the vascular actions of tachykinins. Comparison of ED50 demonstrated a rank order of potency of SP > P .simeq. > K suggesting that the vascular receptor for SP is of the SP-P type. Analysis of the regression lines for log dose of tachykinin vs. percent decrease in diastolic blood pressure revealed similar slopes for SP and E and for P and K. The maximal response caused by P was greater than that caused by SP, E or K. These observations are not consistent with postulated classifications of tachykinins or tachykinin receptors, suggesting that undefined tissue factors may have affected the relative in vivo potencies of these peptides. Apnea occurred with K and E throughout the effective dosage range. SP caused apnea only in doses in excess of those causing maximal vasodilation. P did not cause apnea. These observations suggest that the SP-receptor mediating respiratory depression is of the SP-E type. The SP-antagonists [D-Pro2, D-Phe7, D-Trp9]-SP and [D-Pro2, D-Trp7,9]-SP exhibited cardiovascular activity similar to that caused by SP excepting that recovery did not occur. Threshold doses for depressor actions were 25,000 ng/kg. The response to 100 ng SP/kg was decreased by 25,000 ng/kg of antagonists but unaffected by lower doses. The decreased response probably reflects the deteriorated hemodynamic status of the animal rather than receptor blockade. Higher doses of SP-antagonists resulted in death of the animals.

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