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The study was carried out to investigate the effect of azelastine on the Substance P (SP) concentration in bronchoalveolar (BAL) and nasal (NAL) lavage obtained from atopic grass pollen asthmatics and non-atopic healthy subjects. In BAL and NAL fluids there was a significant elevation in the baseline concentration of SP between asthmatics and volunteers. Allergen provocation induced a rise of SP in BAL and NAL in asthmatics, but not in volunteers. Azelastine pre-treatment resulted in a significant reduction of SP in baseline concentration of SP in BAL and NAL from asthmatics. An elevation of SP in BAL or NAL fluids after allergen provocation was not seen in asthmatics pretreated with azelastine. Azelastine did not influence the SP concentration in BAL and NAL of volunteers.

It was shown in two different provocation models (nasal and bronchial provocation) that substance P (SP) may play an important role in the neurogenic inflammatory response in upper and lower airway disease. (1) Pretreatment with SP augments the antigen challenge response of the nasal mucosa. (2) The baseline bronchoalveolar lavage (BAL) concentrations of SP are elevated 8-fold in allergies (pollen asthma) as compared with normals, even outside of season. (3) The SP concentration in BAL increases significantly (p

In order to evaluate disturbances of the respiratory control in the first year of life in children with a statistically enhanced risk of SIDS, substance P-like immunoreactivity (SPLI) in plasma and mean apnoea duration (MA) were examined. 4 groups of infants were investigated: Controls, full-term infants with anamnestic SIDS-risk factors, preterm infants with additional risk factors and preterm infants without such factors. Infants aged from -4(corrected age) to 63 weeks. SPLI in plasma was determined by a specific, homologous radioimmunoassay. The SPLI-level was significantly higher in controls (n = 41; means +/- SE = 36.37 +/- 4.86 pg/ml) than in preterm infants without (n = 21; 25.41 +/- 5.54 pg/ml) or with additional anamnestic risk factors (n = 111; 25.89 +/- 3.09 pg/ml). SPLI was higher in full-term SIDS-risk infants (n = 150; 30.73 +/- 2.35 pg/ml) than in the preterm groups. There is a significant age dependence in the groups full-term SIDS-risk infants and preterm infants with additional risk factors. During maturation the SPLI-level in plasma rises in these groups from lower values. The MA-values were determined by means of a daytime polygraphy. There is an age dependence of the MA-values during active sleep in full-term SIDS-risk infants and in preterm infants with additional anamnestic risk factors. In the age group 4-17 weeks (peak of SIDS frequency) in active sleep the MA-values were significantly higher in all 3 risk groups than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Stress produced by anaesthesia and operation results in the activation of regulatory processes aimed at maintaining homoeostasis. Numerous studies point to the opioid system acting in the adaptation process as a reserve force in homoeostatic maintenance. We made peri- and intraoperative radioimmunological measurements of the beta-endorphin, a c-terminal fragment of the pro-opiomelanocortin. In spite of the latent stress prevalent in patients before the operation, there was no change in the concentration of beta-endorphin in the plasma before the operation. As soon as the operation began a marked increase in the beta-endorphin concentration was observed, reaching a peak at the end of the operation. Postoperatively, the beta-endorphin level rapidly decreased and the initial value was attained within 24 hours. Our studies provide evidence that there is a protective mechanism guarding the organism against external disturbing factors in stress situations.

In 66 patients who had to undergo radical abdominal hysterectomy because of cancer of the cervix uteri, the plasma concentrations of beta-endorphin were observed intra- and postoperatively. Two anaesthetic techniques were used: neuroleptanalgesia and thoracolumbar epidural analgesia with sedation and controlled inhalation of a mixture of oxygen and nitrous oxide. While the higher dosage of analgesics administered intraoperatively resulted in markedly lower plasma concentrations of beta-endorphin, there was no such effect in the postoperative phase. Patients with epidural analgesia who were absolutely painless postoperatively had, during that stage, higher concentrations of beta-endorphin in the plasma than those patients who had been given neuroleptanalgesia. They had received no analgetic treatment during the postoperative observation period. These differences are attributed to an increased adaptability of patients subsequent to neuroleptanalgesia. The neuronal block can result in a decrease in functional activity of the suprarenal medulla and impair adaptability. The stress-induced opioid analgesia can be suppressed by circulating enkephalin from the suprarenal medulla.

The substance P-like immunoreactivity (SPLIR) of plasma and adrenal medulla from spontaneously hypertensive (SHR) and normotensive WKY rats was measured by a sensitive and highly specific radioimmunoassay for substance P (SP). With increasing age the level of substance P in the adrenal medulla decreased, whereas the SP content of the plasma remained constant in both groups. The SPLIR in plasma of SHR was significantly lower than in normotensive WKY rats. After acute stress the SPLIR, especially of the adrenal medulla of WKY rats, increases, and decreases in SHR. The reason for this different behaviour is discussed and it is assumed that hyperreactions in the sympathetic system may be responsible.

The influence of chronic immobilization on blood pressure and on substance P-like immunoreactivity (SPLIR) in blood plasma was examined in 11-week-old male spontaneously hypertensive rats (SHR) and male normotensive Wistar Kyoto rats (WKY). In SHR chronic immobilization caused a stop of the genetically fixed development of hypertension at the level already reached. Also, SPLIR in blood plasma was lower compared with a SHR control group without immobilization. In WKY rats chronic immobilization has no influence on blood pressure and SPLIR. The observed variations in SPLIR and blood pressure under the influence of chronic immobilization is discussed in relation to a possible function of substance P in the development of hypertension.

Substance P (SP) plays an important role in central nervous and peripheral blood pressure regulation. Its effects include modulating influence on the adrenergic system and inhibition of stress-induced plasma noradrenaline increase in animal studies. In patients with essential hypertension (n = 45, WHO stages 1 and 2) the SP-like immunoreactivity (SPLIR) was found significantly (p less than 0.01) lower (1.36 +/- 0.23 pg/100 microliters) than in 24 normotensive subjects (4.54 +/- 0.72 pg/100 microliters). Furthermore, the influence of a mental stress test on SPLIR was investigated in patients with essential hypertension (n = 11, WHO stage 1) and compared with nine normotensive subjects. Whereas in normotensive subjects plasma SP increased under a standardized mental arithmetic test (4.03 +/- 0.48 to 4.74 +/- 0.56 pg/100 microliters), in hypertensive patients a decrease of SP from lower baseline levels (2.85 +/- 0.54 to 2.57 +/- 0.54 pg/100 microliters) was demonstrated. The significantly different changes of plasma SP in normotensive and hypertensive subjects under mental stress conditions had the opposite direction in comparison with the adrenergic reaction [higher and prolonged increase of plasma noradrenaline (NA) in the hypertensive group]. Under antihypertensive drug treatment with prazosin (4.5 mg/day, n = 10) or with captopril (450 mg/day, n = 10) an increase of plasma SP was registered. The results support the participation of SP in the pathogenesis of human hypertension and in therapeutic mechanisms. Lower plasma levels and decreased responsiveness of SP possibly represent the enhanced stress sensitivity in primary hypertension.

Most research on substance P deals with its presumed function in the nervous system. Both excitatory and inhibitory actions have been observed in pharmacological studies. For example, substance P has a dual action on nociception in mice: it produces analgesia or hyperalgesia, depending on the dose and on the individual sensitivity to pain. This is interpreted to mean that substance P is capable of normalizing responsiveness to pain. Thus substance P could be classified as a regulatory peptide, or 'regulide'. A similar normalizing action of substance P was found in stress-induced disorders of sleep, behaviour and blood pressure in rats. The mechanism of this normalizing action is not yet clear. The decrease in activity observed for dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase in adrenal glands of rats treated with the peptide may serve as a preliminary hypothesis.

Patients with essential hypertension (n = 45) had significantly lower substance P plasma levels (13.6 +/- 2.30 pg/ml) in comparison with a group of 24 normotensive subjects (45.4 +/- 7.18 pg/ml) analyzed by radioimmunoassay. Prazosin treatment for 2 weeks with 4.5 mg/day enhanced the substance P plasma level depending on its antihypertensive effect. Norepinephrine concentration in plasma was also elevated by prazosin. Dipeptidylpeptidase IV, dopamine-beta-hydroxylase and plasma renin activity were not changed significantly. The results indicate the participation of substance P in pathophysiological processes of human essential hypertension.