Substance P-inducing massive postmortem bronchoconstriction in guinea pig lungs

To further examine the role that substance P plays in initiating the observed massive postmortem bronchoconstriction in guinea pig lungs and to explore the role of neural reflex in this airway spasm, six groups of animals were employed: control (n = 6), morphine (n = 6), substance P (n = 5), chronic capsaicin pretreatment + substance P (n = 5), tetrodotoxin (TTX) + acute capsaicin (n = 4), and chlorisondamine + acute capsaicin (n = 5). Pressure-volume curves were performed prior to and following the initiation of artificial pulmonary perfusion with 1% bovine serum albumin and 5% dextran in Tyrode's solution. A decrease in inflation volume (the lung volume between transpulmonary pressure of 0 and 30 cmH2O during inflation) was used as an index of bronchoconstriction. In control animals, inflation volume decreased to 20–30% of the base-line value at 15–30 min of perfusion, indicating massive bronchial constriction during this time period. Morphine (an agent inhibiting substance P release) significantly attenuated the spasm, whereas the presence of substance P in the perfusate markedly enhanced the constriction. Depletion of endogenous substance P by chronic capsaicin pretreatment did not affect exogenous substance P-induced spasm. Acute capsaicin-induced bronchoconstriction was significantly attenuated by TTX but was not affected by the ganglionic blocking agent, chlorisondamine. These data suggest that substance P initiates the massive postmortem bronchoconstriction in guinea pig lungs and that substance P is released by local stimulation of sensory nerve endings via axonal reflex.

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Tachykinin recovery during postmortem bronchoconstriction in guinea pig lungs

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.3.1215 ◽

1991 ◽

Vol 70 (3) ◽

pp. 1215-1219 ◽

Cited By ~ 7

Author(s):

M. A. Martins ◽

S. A. Shore ◽

J. M. Drazen

Keyword(s):

Substance P ◽

Guinea Pig ◽

Neutral Endopeptidase ◽

Neurokinin A ◽

Opening Pressure ◽

Airway Opening ◽

Isolated Lungs ◽

Peak Value

We examined the role of substance P (SP) and neurokinin A (NKA) in the postmortem bronchoconstriction in guinea pig lungs using isolated lungs superfused via the trachea. Airway opening pressure (Pao) during superfusion was monitored and the superfusate collected for analysis of SP- and NKA-like immunoreactivities (SP-LI and NKA-LI, respectively). Peak Pao (39.0 +/- 3.9 cmH2O) was reached 10 min after starting superfusion; Pao decreased slowly thereafter, reaching only 9.9 +/- 2.2% of the peak value 2 h after starting superfusion (P less than 0.005); 12.6 +/- 2.6 and 34.0 +/- 9.7 fmol of SP-LI and NKA-LI, respectively, were found in the fraction corresponding to 10-20 min of superfusion. Recovered immunoreactivities decreased to 5.2 +/- 0.3 and 9.3 +/- 1.8 fmol of SP-LI and NKA-LI, respectively, in the fraction corresponding to 110-120 min of superfusion (P less than 0.05). Inhibition of neutral endopeptidase with thiorphan resulted in significantly greater increases in Pao (P less than 0.005) and augmentation of the recovery of SP-LI and NKA-LI (P less than 0.05 and P less than 0.001, respectively). Capsaicin treatment of animals 7-10 days before the removal of their lungs abolished the increase in Pao during superfusion and resulted in a significant decrease in the amount of SP-LI and NKA-LI recovered. Our data confirm that tachykinin release occurs during postmortem bronchoconstriction in guinea pig lungs and, furthermore, that tachykinin degradation by NEP modulates the intensity of this response.

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Neurogenic Control of Cerebral Circulation

Cephalalgia ◽

10.1177/03331024850050s205 ◽

1985 ◽

Vol 5 (2_suppl) ◽

pp. 25-33 ◽

Cited By ~ 27

Author(s):

G Burnstock

Keyword(s):

Substance P ◽

Sensory Nerve ◽

Sympathetic Nerves ◽

Purine Nucleotides ◽

Axon Reflex ◽

Calcitonin Gene ◽

Perivascular Nerves ◽

Neuromuscular Apparatus ◽

Perivascular Nerve Plexus

The cerebral vascular neuromuscular apparatus consists of a varicose perivascular nerve plexus at the adventitial-medial border and smooth muscle cells in the medial coat that are functionally connected. In addition to noradrenaline and acetylcholine, a number of putative non-adrenergic, non-cholingergic neurotransmitters have been identified in cerebral perivascular nerves, including serotonin, substance P, vasoactive intestinal polypeptide, gastrinreleasing peptide, cholecystokinin, somatostatin, neurotensin, calcitonin gene-related peptide and neuropeptide Y. The role of adenosine-5'-triphosphate as a cotransmitter with noradrenaline in some perivascular sympathetic nerves, and of endothelial cells in mediating the vasodilatation produced by some neurohumoral agents is discussed. Speculations are made about the relation between vascular neuroeffector mechanisms and migraine, including the possiblity of local vasospasm by serotoninergic nerves, reactive hyperaemia involving purine nucleotides and nucleosides, release of substance P from sensory nerve collaterals during antidromic ('axon reflex') impulses and secondary release of local agents such as prostanoids, histamine and bradykinin.

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Substance P-induced inflammatory responses in guinea-pig skin: The effect of specific NK1 receptor antagonists and the role of endogenous mediators

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1995.tb13354.x ◽

1995 ◽

Vol 114 (7) ◽

pp. 1343-1350 ◽

Cited By ~ 53

Author(s):

Desmond T. Walsh ◽

Vivian B. Weg ◽

Timothy J. Williams ◽

Sussan Nourshargh

Keyword(s):

Substance P ◽

Guinea Pig ◽

Inflammatory Responses ◽

Nk1 Receptor ◽

Receptor Antagonists ◽

Pig Skin ◽

Nk1 Receptor Antagonists

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Airway neutral endopeptidase-like enzyme modulates tachykinin-induced bronchoconstriction in vivo

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.6.2585 ◽

1988 ◽

Vol 65 (6) ◽

pp. 2585-2591 ◽

Cited By ~ 77

Author(s):

D. J. Dusser ◽

E. Umeno ◽

P. D. Graf ◽

T. Djokic ◽

D. B. Borson ◽

...

Keyword(s):

Substance P ◽

Guinea Pig ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Guinea Pigs ◽

Vagus Nerve Stimulation ◽

Neutral Endopeptidase ◽

Base Line ◽

Pulmonary Resistance

To determine whether neutral endopeptidase (NEP), also called enkephalinase (EC 3.4.24.11), modulates the effects of exogenous and endogenous tachykinins in vivo, we studied the effects of aerosolized phosphoramidon, a specific NEP inhibitor, on the responses to aerosolized substance P (SP) and on the atropine-resistant response to vagus nerve stimulation (10 V, 5 ms for 20 s) in guinea pigs. SP alone (10(-7) to 10(-4) M; each concentration, 7 breaths) caused no change in total pulmonary resistance (RL, P greater than 0.5). Phosphoramidon (10(-4) M, 90 breaths) caused no change either in base-line RL (P greater than 0.5) or in the response to aerosolized acetylcholine (P greater than 0.5). However, in the presence of phosphoramidon, SP (7 breaths) produced a concentration-dependent increase in RL at concentrations greater than or equal to 10(-5) M (P less than 0.001). Phosphoramidon (10(-7) to 10(-4) M; each concentration, 90 breaths) induced a concentration-dependent potentiation of SP-induced bronchoconstriction (10(-4) M, 7 breaths; P less than 0.01). Vagus nerve stimulation (0.5-3 Hz), in the presence of atropine, induced a frequency-dependent increase in RL (P less than 0.001). Phosphoramidon potentiated the atropine-resistant responses to vagus nerve stimulation (P less than 0.001) at frequencies greater than 0.5 Hz. The tachykinin antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P abolished the effects of phosphoramidon on the atropine-resistant response to vagus nerve stimulation (2 Hz, P less than 0.005). NEP-like activity in tracheal homogenates of guinea pig was inhibited by phosphoramidon with a concentration producing 50% inhibition of 5.3 +/- 0.8 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

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Beta 2-adrenoceptor agonists inhibit NANC neural bronchoconstrictor responses in vitro

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.3.1195 ◽

1993 ◽

Vol 74 (3) ◽

pp. 1195-1199 ◽

Cited By ~ 21

Author(s):

G. M. Verleden ◽

M. G. Belvisi ◽

K. F. Rabe ◽

M. Miura ◽

P. J. Barnes

Keyword(s):

Substance P ◽

Guinea Pig ◽

Electrical Field Stimulation ◽

Sensory Nerves ◽

Inhibitory Effects ◽

Exogenous Substance ◽

Dependent Inhibition ◽

Adrenoceptor Agonists ◽

Beta 2

Nonadrenergic noncholinergic (NANC) contractile responses in guinea pig bronchi are due to the release of tachykinins from airway sensory nerves. The purpose of this study was to determine whether beta 2-receptor agonists modulate NANC contractions in guinea pig bronchi in vitro. Bronchial rings were suspended in organ baths for isometric measurement of tension, and comparable contractions were induced by electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) or by exogenous substance P (3 microM). Aformoterol and salbutamol produced concentration-dependent inhibition of the NANC contraction, with aformoterol being ninefold more potent than salbutamol; approximate 50% inhibitory concentrations for aformoterol and salbutamol were 1.03 nM (n = 6) and 9.3 nM (n = 6), respectively. Aformoterol also inhibited the contraction induced by exogenous substance P but to a far lesser extent than its inhibition of EFS-induced responses. The inhibitory effects of formoterol (10 nM) on responses to EFS at 8 Hz were significantly prevented by propranolol (1 microM) and ICI 118551 (a beta 2-antagonist, 0.1 microM) but not by atenolol (a beta 1-antagonist, 1 microM) or phentolamine (10 microM). These experiments demonstrate that beta 2-agonists may modulate the release of tachykinins from airway sensory nerves by prejunctional receptors.

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Area postrema: essential for support of arterial pressure after hemorrhage in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.6.r1472 ◽

1990 ◽

Vol 258 (6) ◽

pp. R1472-R1478 ◽

Cited By ~ 1

Author(s):

K. M. Skoog ◽

M. L. Blair ◽

C. D. Sladek ◽

W. M. Williams ◽

M. L. Mangiapane

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Data Acquisition ◽

Area Postrema ◽

Plasma Renin ◽

Base Line ◽

Sprague Dawley ◽

Time Period ◽

Sprague Dawley Rats

Previous studies have indicated that the area postrema (AP) of the rat is necessary for the development of chronic angiotensin-dependent hypertension. The present study assesses the role of the AP in the maintenance of arterial pressure during hemorrhage. Sprague-Dawley rats were given sham or AP lesions 1 wk before the experiment. They were instrumented with femoral arterial and venous catheters 2 days before the experiment. On the day of the experiment, base-line mean arterial pressure (MAP) was measured for 1 h before hemorrhage. During the following 45 min, each rat was subjected to one 7-ml/kg hemorrhage every 15 min for a total of three hemorrhages. MAP was monitored by computerized data acquisition. As shown previously, MAP was slightly but significantly lower in AP-lesion rats compared with sham-lesion rats before the hemorrhage procedure. In AP-lesion rats, hemorrhage resulted in a significantly greater fall in arterial pressure than in sham-lesion rats. In spite of larger drops in pressure in AP-lesion rats, hemorrhage caused equivalent increases in plasma renin and vasopressin in both groups. In AP-lesion rats compared with sham-lesion rats, significant bradycardia was present before hemorrhage. Hemorrhage caused bradycardia in both sham- and AP-lesion rats relative to the prehemorrhage heart rates, but AP-lesion rats showed greater bradycardia than did sham-lesion rats during every time period. We conclude that the AP may play an important role in the defense of arterial pressure against hemorrhage.

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