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Biomedical subjects

G N Colasurdo

Publications and source records attributed to G N Colasurdo.

7 recordsLinked to original sources

Modulation of acetylcholine release in rabbit airways in vitro.

We investigated the effects of substance P (SP) and vasoactive intestinal peptide (VIP) on acetylcholine (ACh) released from nerve endings by electrical field stimulation (EFS) in rabbit airways in vitro. ACh release was directly measured using high-performance liquid chromatography with electrochemical detection. Airway smooth muscle (ASM) segments, dissected from the midtrachea down to the left mainstem bronchus, were obtained from New Zealand White rabbits and mounted in organ baths containing modified Krebs-Henseleit solution, physostigmine, and choline. EFS at 20 Hz was delivered for 15 min to define baseline ACh release (pmol per gram of tissue per minute). There were no significant regional differences in ACh release during these baseline studies. A second stimulation was then performed in the absence (control) and presence of one or more of the following substances: SP (10(-7) M), a nonpeptide antagonist of the NK1 receptor (10(-7) M CP-96,345; Pfizer), and VIP (10(-7) M). Results for ACh release are expressed as a percentage of the first stimulation (means +/- SE). SP significantly increased ACh release in all ASM segments. This effect was abolished by CP-96,345. VIP alone did not affect ACh release. However, it significantly decreased SP-induced ACh release in all ASM segments. We conclude that SP significantly increases ACh release, thus facilitating cholinergic neurotransmission; its effect is abolished by CP-96,345. VIP decreases SP-induced ACh release, indicating a modulatory effect on cholinergic neurotransmission.

Acetylcholine

Human respiratory syncytial virus affects nonadrenergic noncholinergic inhibition in cotton rat airways.

A dysfunction of the nonadrenergic noncholinergic inhibitory (NANCi) system has been invoked as a possible mechanism underlying or contributing to altered airway function. In the present study we assessed whether human respiratory syncytial virus (HRSV) infection affects the airways' neurally mediated contractile and relaxant (NANCi) responses in vitro. NANCi responses were studied on tracheal smooth muscle (TSM) segments obtained from young adult cotton rats, a well-established model for HRSV infection. To assess NANCi responses, TSM segments were removed and placed in tissue baths containing modified Krebs-Henseleit, atropine (1 x 10(-6) M) and propranolol (5 x 10(-6) M). After contraction with neurokinin A (1 x 10(-5) M), electrical field stimulation (EFS) was applied at stimulation frequencies ranging from 5 to 30 Hz. The NANCi responses were measured and expressed as the mean (+/- SE) percent relaxation. To evaluate neurally mediated contractile responses, full frequency response curves (0.5-30 Hz) to EFS were also performed. We found significantly decreased NANCi responses in TSM segments obtained from infected cotton rats (n = 12) compared with control animals (n = 9) (P < 0.002). Furthermore, the contractile responses to EFS were increased in infected animals compared with the control group (P = 0.0001). These findings demonstrate that HRSV infection leads to an enhanced contractile response to EFS and a significant decrease in NANCi response in cotton rat airways in vitro. This disruption of the neural control of airways may lead to the development of altered airway function.

Animals

SP-induced contraction of airway smooth muscle in normal and allergen-sensitized rabbits: mechanism of action.

We studied the mechanisms involved in the airway smooth muscle (ASM) contraction to substance P (SP) in normal (control) and allergen-sensitized (immune) rabbits as well as immune rabbits exposed to allergen via the airways (immune challenged). Cumulative concentration-response curves to SP (1 x 10(-9) to 1 x 10(-4) M) were performed in ASM segments in the absence and presence of atropine (10(-5) M) in vitro. The maximal contractile response (g tension/g tissue) at 10(-4) M SP and ASM contractions at various concentrations of SP were expressed as means +/- SE. We found no difference in the contractile response to SP between control and immune animals. ASM segments obtained from immune-challenged rabbits were more responsive to SP. Atropine shifted to the right the concentration-response curves and decreased the maximal ASM contraction at 10(-4) M SP in all three groups; this effect, however, was greater in immune-challenged tissues. These findings demonstrate an increased contractile response to SP in immune-challenged animals mediated by a more pronounced facilitation of cholinergic neurotransmission. We conclude that the final ASM response to SP is the result of a complex interaction between direct effects on ASM and indirect effects through modulation of cholinergic neurotransmission.

Allergens

Decrease in the airways' nonadrenergic noncholinergic inhibitory system in allergen sensitized rabbits.

A decrease in the airways' nonadrenergic noncholinergic inhibitory (NANC-i) system is one of the mechanisms that may contribute to allergen-induced changes in neural control within airways. We measured the airways' neurally mediated contractile and relaxant (NANC-i) responses in tracheal segments and left mainstem bronchus (LMB) from normal (control), immune (ragweed sensitized), and immune challenged rabbits. Immune rabbits were sensitized to mixed ragweed extract through parenteral injections from birth, while the immune challenged group had an additional airway exposure to aerosolized ragweed 48 hours prior to the in vitro studies. Neurally mediated contractile responses to electrical field stimulation (EFS) were increased in the immune challenged group, with the increase most significant in tracheal smooth muscle at a stimulation frequency of 20 Hz. To assess NANC-i responses, airway smooth muscle (ASM) segments from these groups were placed in tissue baths containing atropine (10(-6) M) and propranolol (5 x 10(-6) M). After contraction of the tissue with neurokinin A (NKA, 10(-5) M), the NANC-i response to EFS at 20 Hz was measured and reported as the mean (+/- SEM) percent relaxation. No significant differences were seen in the contractile responses of ASM segments to NKA among the three groups. The tracheal segments showed a significantly different NANC-i relaxation response among all groups: in the control group, 29.1 +/- 3.7; in the immune group 15.8 +/- 2.3%; and in the immune challenged group, 2.1 +/- 4.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens

Maturation of nonadrenergic noncholinergic inhibitory system in normal and allergen-sensitized rabbits.

We investigated the functional existence of the nonadrenergic noncholinergic inhibitory (NANCi) system in developing rabbit airways in vitro. Furthermore, we evaluated the effect of parenteral exposure to a specific allergen (ragweed) on the maturation of this neural pathway. NANCi responses were studied on tracheal smooth muscle (TSM) segments obtained from normal and ragweed-sensitized New Zealand White rabbits at 1, 2, 4, and 12 wk of age. The TSM segments were removed and placed in tissue baths containing modified Krebs-Henseleit solution, atropine (1 x 10(-5) M), and propranolol (5 x 10(-6) M). After contraction with neurokinin A (1 x 10(-5) M), electrical field stimulation was applied at stimulation frequencies ranging from 5 to 30 Hz to determine the frequency that produced maximal relaxation. The NANCi response to EFS was measured and expressed as the mean (+/- SE) percent relaxation at 20 Hz, because this stimulation frequency gave the maximal NANCi response at each age studied. TSM segments obtained from control rabbits at 1 wk of age did not demonstrate a NANCi response at the frequencies of stimulation used. By contrast, a reproducible NANC relaxation was demonstrated in TSM from 2-, 4-, and 12-wk-old rabbits. The magnitude of this response was 27 +/- 4.7 (n = 10), 29 +/- 4.8 (n = 9), and 37 +/- 4% (n = 18), respectively. The same experiments performed on TSM segments obtained from ragweed-sensitized animals gave significantly decreased values of NANCi response. In 2-, 4-, and 12-wk-old rabbits, the NANCi responses were 11.5 +/- 3.4 (n = 9), 11 +/- 2 (n = 13), and 16 +/- 4.2% (n = 14).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Day/night variations of airway reactivity after drug premedication.

Seventeen asthmatic, non-atopic patients (aged 15-48 years) were studied at different hours of the day. On 3 different days, they were submitted to a fog-test at 03:00 p.m. and at 03:00 a.m. On 2 different days, they were given fenoterol (200 micrograms) or Duovent (fenoterol 200 micrograms plus ipratropium bromide 80 micrograms). We were able to demonstrate significant inter-hour differences of the basal values of all parameters, except FVC, in all patients at 03:00 p.m. and at 03:00 a.m. We did not observe any inter-hour difference after the fog-test. Both fenoterol and Duovent improved challenge-induced bronchoconstriction. After the fog-test, both drugs showed an inter-hour variability of ventilatory parameters, which was not significant without drugs because it was masked by the magnitude of the obstructive response to challenge.

Adolescent