Substance P-immunoreactive sensory nerves in the lower respiratory tract of various mammals including man

IVarious doses of mediators were tested on tracheal vascular resistance in dogs anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. 2 All drugs produced dose-related changes in vascular resistance. 3 The peptides bradykinin, substance P and vasoactive intestinal peptide (VIP) each had similar vasodilator potencies and were much more powerful than histamine, methacholine and salbutamol.4 Platelet activating factor (Paf) was a weaker dilator than the peptides. Prostaglandins D2, E, and F2,, had wide dilator potency ranges, PGE, being very effective even at low concentrations.5 Phenylephrine, an a-adrenoceptor agonist, was the only drug tested that always increased vascular resistance. 6 All the drugs studied also had effects on the contralateral tracheal vascular resistance.

Section: Discussionmentioning

confidence: 98%

Dose‐related effects of pharmacological mediators on tracheal vascular resistance in dogs

Laitinen

Widdicombe

1987

“…Substance P (SP) is a potent neuropeptide present in airway sensory nerves of several species including guinea-pigs and man, and found in close relation to the airway smooth muscle, beneath and within the epithelium, around ganglion cells and around blood vessels in the airway interstitium (Lundberg et al, 1984b). SP is a potent mediator of smooth muscle contraction, mucus secretion and microvascular leakage in airways of several species (Lundberg et al, 1983;1984a;Coles et al, 1984;Lotvall et al, 1989), and has been implicated in the pathogenesis of asthma (Barnes, 1986) and in bronchial hyperreactivity induced by respiratory viral infections (McDonald, 1988) or toluene diisocyanate (Sheppard & Scypinski, 1988).…”

Section: Introductionmentioning

confidence: 99%

Effects of aerosolised substance P on lung resistance in guinea‐pigs: a comparison between inhibition of neutral endopeptidase and angiotensin‐converting enzyme

Lötvall

Skoogh

Barnes

et al. 1990

1We have examined in guinea-pigs, in vivo, the effects of inhibition of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the airway response to aerosolised substance P (SP). We aerosolised captopril (4.6mM, 60 breaths; 210nmol) to inhibit ACE and acetorphan (0.3, 1 and 3mM, 60 breaths; 9nmol, 33nmol and 110nmol respectively) to inhibit NEP. We also examined the effect of the highest dose of acetorphan (110 nmol) on the response to aerosolised acetylcholine (ACh).2 Responsiveness to SP (or ACh) was measured as the change in lung resistance (RL) induced by nebulisation of increasing concentrations of SP (or ACh) before and after treatment with the inhibitor. PC200, defined as the provocative concentration inducing an increase in RL of 200% above baseline, was calculated for each challenge. 3 Administration of acetorphan before the second SP-challenge induced a dose-dependent decrease in PC200 for SP amounting to 1.8 (± 0.3) log units after treatment with 11 nmol acetorphan. Treatment with vehicle before the second SP-challenge or with 3 mM acetorphan before the second ACh-challenge had no significant effect on PC200. 4 Treatment with captopril (21 nmol) induced only a small, nonsignificant leftward shift of PC200 to SP (0.3 + 0.2 log units). 5 We conclude that a NEP-like enzyme, but not ACE, regulates the response to aerosolised SP. We suggest that the same is true for SP released endogenously from sensory nerve endings in the airway epithelial layer.

“…SP is present in afferent nerves in the airways of several species, including guinea-pigs and man (Nilsson et al, 1977;Lundberg et al, 1984;Polak & Bloom, 1986) and SP-immunoreactive neurones have been identified in the vagus nerve (Gamse et al, 1979). SP and other tachykinins have been shown to cause contraction of human and guinea-pig airways in vitro (Mizrahi et al, 1982;Lundberg et al, 1983) and in vivo (Andersson & Persson, 1977;Goel & Biggs, 1986).…”

Section: Introductionmentioning

confidence: 99%

Facilitation by tachykinins of neurotransmission in guinea‐pig pulmonary parasympathetic nerves

Hall

Barnes

Meldrum

et al. 1989

1 The effect of tachykinins on cholinergic neurotransmission was studied in an innervated tracheal tube preparation isolated from guinea-pigs anaeshetized with urethane. These results suggest that tachykinins act on NK2 receptors, both on the trachealis muscle and on postganglionic pulmonary parasympathetic nerve terminals. Activation of the neuronal receptors may increase the probability of transmitter release from the nerve terminals.