The effect of tachykinins on sheep bronchomotor tone

Abstract

SUMMARYThe mammalian tachykinin neuropeptides substance P (SP) and neurokinin A (NKA) are present in the airways of several species and are involved in control of bronchomotor tone. We investigated the effect of SP and NKA on various respiratory and cardiovascular parameters in anaesthetized sheep. Dose-dependent decrease in dynamic compliance (CdYf) and increase in respiratory resistance (RL) occurred with intravenous administration of SP. The predominant effect of NKA was on Cdyn with little or no effect on RL. Consequently SP is a more potent bronchoconstrictor than NKA in the sheep and affects both central and peripheral airway tone. The sensitivity to SP and NKA and the order of potency found suggests the NK-1 receptor predominates in sheep airways. Atropine and the ganglion blocker hexamethonium markedly reduced the bronchoconstriction caused by SP. SP and NKA were equipotent in causing a significant reduction in respiratory rate. SP caused a fall in mean blood pressure while NKA caused mild vasoconstriction. Neither peptide affected heart rate. We concluded that SP is a more potent bronchoconstrictor than NKA in the sheep and that the mechanism of action is mainly indirect involving modulation of postganglionic cholinergic nerve endings.

Tachykinin‐induced bronchoconstriction in sheep is NK‐1 receptor mediated and exhibits tachyphylaxis

“…These findings clearly have important implications for the design of studies examining the effects of drugs or other interventions on the response to SP, as results will be confounded by tachyphylaxis if insufficient time is allowed between baseline and post‐intervention SP doses. For example, one report examined the effect of atropine on SP responses only 20 min after the index SP dose and only 1 h after an SP dose response study 11 . No comment was made regarding tachyphylaxis in this study, although the transient nature of the response to SP was similar to our findings.…”

“…Unlike some previous reports we did not find that SP had any significant effect on blood pressure, therefore none of the responses detected were confounded by reflex responses to hypotension. Although the effect of inhaled SP was investigated in preliminary experiments, like Abraham et al we found no significant effect 9–11 . However, this was not the focus of the current study and the negative results obtained were possibly due to the low dose of SP.…”

The role of vagal pathway andNK1andNK2receptors in cardiovascular and respiratory effects of neurokinin A

“…Experimental data are not uniform. The effect of NKA on HR and mean blood pressure was not observed in anaesthetized sheep and conscious rats . However, in conscious humans an increase in HR was reported without influence on blood pressure .…”

“…The drop in V T corresponds somewhat to the early response observed by us, but lacks further augmentation. Dose‐dependent reduction in respiratory rate with steady tidal volume evoked by an intravenous NKA was described in anaesthetized sheep . It is presumed that the disparities are associated with the route and dose of NKA application, species differences and application of anaesthesia.…”

Distribution of Substance P Receptor (Neurokinin-1 Receptor) in Normal Ovine Lung and During the Progression of Bronchopneumonia in Sheep

“…These studies underscore the lack of complete correlation between the anatomic distribution of receptors and SP-like nerve fibers in the lung of various species, indicating the importance of revealing the distribution of NK-1R, particularly in attempting to understand the neuropeptide's mechanisms of action and functions. Corcoran and Haigh (1992) have suggested that NK-1R predominates in sheep airways compared to other NK receptors. Therefore, the first aim of our study was to assess NK-1R distribution in the lung of healthy weaned lambs and to compare its immunoreactivity with various stages of pneumonia caused by the ovine pathogen M. haemolytica (Ramirez-Romero et al 2001) during the 45-day period.…”