Comparison of the bronchoconstrictor and cardiovascular effects of some tachykinins in guinea pigs

Abstract

The effects of three tachykinins [substance P (SP), physalaemin (PH), and eledoisin-related peptide (ERP)] were investigated in anesthetized paralyzed guinea pigs. We measured airway resistance (R) and dynamic thoracic elastance (E) with a computerized technique, and blood pressure via a carotid artery. Tachykinins injected iv or intra-aortically (ia) induced dose-dependent increases in R and E, 4 times greater on iv than ia injection. They did not give rise to tachyphylaxis. As a bronchoconstrictor, PH was 5.0X and ERP 1.8X more potent than SP; time to peak response was longer for PH than for ERP and SP; and hypotensive responses, which were of similar magnitude for all three substances, lasted longest after PH. Bronchoconstrictor responses were unaltered by bilateral vagotomy, atropine, mecamylamine, and mepyramine. Morphine reduced PH-induced increases in R (P <0.01) and E (P <0.05), which were not reversed by naloxone, and capsaicin treatment 1 week before the experiments reduced both SP- and PH-induced increases in E (P <0.05). [D-Pro 2,D-Trp 7,9]-SP reduced ERP-induced increases in R and E, and [D-Arg 1,D-Pro 2,D-Trp 7,9,Leu 11]-SP reduced both SP- and PH-induced increases in R and E. We conclude that PH is the most potent bronchoconstrictor of the tachykinins tested. Tachykinin-induced bronchospasm is ‘non-reflex’ arising via a direct effect on airway smooth muscle; the release of histamine, acetylcholine, or other tachykinins is not involved in the responses. [D-Pro 2,D-Trp 7,9]-SP is more effective at SP-E receptors, and [D-Arg 1,D-Pro 2,D-Trp 7,9,Leu 11]-SP at SP-P receptors; both types of receptor are located all along the airways.