الفهرس 
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Abstract
The beta adrenoceptor function was studied in the atopic d non-atopic asthmatic patients to investigate its role in A. and in the refractory period. The function of beta ceptors was assessed by measuring the change in circulatory eart rate and diastolic blood pressure) and metabolic (blood ucose, plasma free fatty acids and cAIJP) parameters following. travenous infusion of 0.16 mg/kg of Orciprenaline >eta stimulant). •
enty asthmatic patients (10 males and 10 females) and 10
rmal controls (5 males and 5 females) were conducted to
is study. The asthmatic patients were asymptomatic at
e time of study. They were classified into mild (12 patients),
derate (4 patients) and severe (4 patients) according to
.e clinical severity score of Brooks. All medications,
:cept xanthine derivatives, were withheld for at least one
■ek before the study. ”
The following investigations were carried out : Determination of the baseline pulmonary functions (JVC,
mlt FEvywc %t FSF25_75%).
Determination of the atopic state of asthmatic subjects by Prick skin test.
On the first day, the B2 adrenoceptor responsiveness was assessed during rest in both atopic and non-atopic asthmatics and in the control group.
On the second day, cyclo-ergometric stepped steady state exercise was performed according to the recommendations of the 3ronchoprovocationCommittee, American Academy of Allergy. FEV, was recorded at 5, 10 and 15 minutes after exercise to determine the maximum post-exercise broncho-constriction. Then, immediately afterwards, we assessed the function of the B? adrenoceptors.
. On the third day, each subject performed the same exercise twice with an hour interval between each one. The percent reduction in FEV, after each exercise was recorded. The difference between the two reductions in FEV, expressed as a percentage of the reduction after the first exercise was known as the percent protection. When the percent protection was equal or more than -50% the patient was considered refractory and vice versa. Accordingly, our asthmatic subjects were classified into refractory (13 patients) and non-refractory (7’patients). The responsiveness of beta-adrenoceptors was also assessed during the refractory period.
The mean + SD of the data in each group was calculated ’ and t’he statistical significance was estimated by
. student ”t” test for any variable.
The baseline pulmonary functions of the asthmatics
during remission did not differ significantly from those
of the normal controls except in FEV,/FVC% and FEF„C r70^
(expressed as percent predicted). .
All the measured pre-infusion resting parameters were
similar in asthmatic and normal subjects except cAMP level
7/hich was significantly lower in the atopics when compared
with the normal controls.
During rest, the asthmatics especially the atopics and exercise-responders exhibited certain hyporesponsiveness of the Bp adrenoceptors, as assessed by the response to Orciprenaline infusion. This was evidenced by the signifi¬cantly lower response’in the following parameters when compared with the response of the normal control group :
1. The mean increase in heart rate was 30.2+4.89 beats/min in asthmatics, 29.33+4.46 in atopics and 29.77+5.43 in exercise-responders (P<0.05 in all).
2. The mean increase in blood glucose was 18.67+5.75 mg/dl in asthmatics (P<0.01), 21.33+4.7 in atopics (P<0.05), 14.66+4.97 in non-atopies (P<0.01)-, and 17.89+5.02 in exercise-responders (P<0.01).
3. Plasma free fatty acids increase was 148.83+42.6 mBq/L
in asthmatics (P<0.01), 148.8+51.4 in atopics (P<0.05),
148.86+27.63 in non-atopies (P<0.01) and 132.26+25.99
in non-responders (P< 0.001). ,
Diastolic blood pressure and cAMP did not demonstrate a significantly different response in the asthmatics during
rest than in the control group.
«
After the first exercise, Bp adrenoceptors hyporesponsiv-ness was more pronounced- This was demonstrated by the -significantly lower response in the following parameters when compared with the corresponding resting responses:
1. The mean increase in heart rate was 30.2+2.15 beats/min. in normals (P<0.05), 25.7+7.01 in asthmatics and 24.17+6.55 in atopics (P<0.05 in both).
2. Blood glucose increase after infusion was 17.18+8.17 mg /dl in normals (P<0.01), 13.13+5 in asthmatics (P<0.01), 14.03+5.76 in atopics (P<0.001) and 11.55 + 3.52 in exercise-responders (P<0.01).
3. Plasma free fatty acids increase was 148.04+31.95 mBq/L
in normals (P<0.01), 99.62+32.58 in asthmatics (P<0.001), 98.13+33.53 in atopics (P<0.01), 101.85+33.25 in non-atopies (P<0.01), 102.78+35.97 in exercise-responders (P<0.01) and 93.74+26.7 in non-responders (P<0.01).
4. The mean increase in cAI.IP was 5.73+2.07 nmol/L in
normals (P<0.01), 3.32+2.45 in asthmatics (P<0.001),
2.93+1.81 in atopics (P<0.001), 3.24+2.56 in exercise-
responders (P<0.001) and 3«48_+2.4 in non-responders
(P<0.05). • . ■
Slight hyporesponsiveness, less than in asthmatics, was present in the control group. This can explain the
impereeptable bronchoconstriction occuring in them after
the first exercise.
After two consecutive exercises a remarkable amelioration of the 32 adrenoceptor responsiveness was observed. This was observed by the significantly higher response in the following parameters when compared with the corresponding responses after the first exercise :
The mean blood glucose increase was 25.93+5.71 mg /dl in normals (P<0.01), 22.32+8.62 in asthmatics (P<0.001), 1978+4.91 in atopics (P<0.01), 26.13+11.67 in non-atopies (P<0.001) and 24.69+9.44 in exercise-responders (P<0.001).
1. The mean increase in plasma free fatty acids was 196.65+ 36.92 mEq/L in normals (P<0.01), 190.22+57.31 in asthmatics (P< 0.001), 169.68_+49-33 in atopics (P<0.001), 221.04+57.27 in non-atopies (P<0.001), 203.52+53.1 in exercise-responders (P<0.001) and 165.53+.60.54 in non-responders (P<0.05).
2. The mean cAIvIP increase was 11.4+3.04 nmol/L in normals 8.95+5.24 in asthmatics, 10.41+6.01 in atopics and 9.35+4.6 in exercise-responders (P<0.001 in all).
Interestingly, the responsiveness of the beta receptors,
4
as assessed by the cAMP response to Orciprenaline infusion, was significantly lower in the non-refractory asthmatics
(6.84+3.26) when compared with the normal subjects (11.4.+3.04) (P<0.05). However, the responsiveness was similar in the refractory asthmatics (10.09+5.84) and. the normal controls.
We concluded from the present study that exercise, in general, leads to certain hyporesponsiveness of the B? adrenoceptors. The exaggerated hyposensitivity of the B receptors in asthmatics plays an important role, at least in part, in the pathophysiology of EIA.
On the other hand, the improvement of B2 adrenoceptors sensitivity after the second exercise may explain, at least partly, the phenomenon of the refractory period.