Beta-blocking relaxant effects on 5-HT induced vascular smooth contractions

This paper describes the effects of the B-adrenergic antagonists betaxolol and timolol on contractions induced by 5-HT in the rat aortic strip. Aortic strips were incubated in an aerated tissue bath containing Kreb's solution and maintained at 37 degree C. A dose response relationship was elicited with 5-HT. We used 0.5 * 10 M 5-HT as a working dose which gave an equivalent contractile response as 30 * 10 M KCL. The relaxant effects of betaxolol and timolol on the tissue precontracted with 5-HT were studied in equimolar doses ranging from 100 * 10 M to 400 * 10 M. Responses with 5-HT were fitted on a dose-response curve with an ED of 1.66 * 10 M. In the presence of equimolar concentrations of timolol and betaxolol (150 * 10 M) the 5-HT response curve shifted to the right displaying competitive antagonism with both betaxolol and timolol. In the presence of betaxolol the Ed of 5-HT was three-fold higher than with timolol, indicating its higher potency and sensitivity at 5-HT receptors. Timolol and betaxolol both significantly anatagonize serotonin induced vasconstriction. THe increase in relaxation demonstrated by betaxolol may be effect through 5-HTIA receptor subtype; this auto regulatory receptor inhibits the vasoconstrictive effect of serotonin. the differential potencies of betaxolol and timolol in antagonizing the vasoconstrictive effects of serotonin suggests the vascular relaxation may be exerted through receptors other than the adrenergics.(AU)

Evidence that guanylate cyclase is involved in modulating the resting tension and neurally induced contraction of the guinea pig tracheal muscle

Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-lmethylxanthine, which promotes cyclic guanosine monophospate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle(AU)

Activation of guanylate cyclase in the guinea-pig trachea reduces contractile responses of the smooth muscle

Guinea-pig tracheal strips were used to investigate whether activation of guanylate cyclase in the trachea can reduce the contractile response of the smooth muscle. Guanylate cyclase was activated by glyceryl trinitrate and a combination of sodium nitrite and ascorbic acid. These activators inhibited tracheal smooth muscle contractions produced by acetylcholine histamine and electrical field stimulation. However, in the presence of methylene blue, a guanylate cyclase inhibitor, tracheal smooth muscle contractions were not inhibited by the activators. But, in the presence of propranolol, which blocked inhibition mediated by beta-adrenoceptor, both glyceryl trinitrate and the sodium nitrite/ascorbic acid combination were still capable of inhibiting tracheal smooth muscle contractions. Additionally, methylene blue inhibited tracheal smooth muscle relaxation that was electrically induced. These results suggest that the inhibitory action mediated by activated guanylate cyclase may be a mechanism for regulating tracheal smooth muscle contractile reponses (AU)

Bronchomotor tone in protein-energy malnutrition

The study examined the reactivity of the tracheobronchial tree of rats maintained on low protein and tryptophan-deficient diets. It was found that: (1) Rats maintained on 5 percent protein or triptophan-deficient diets showed little or no weight gain. A 15 percent protein diet was adequate for normal growth of female rats, but not of male rats. (2) Airways of malnourished rats showed significant bronchoconstriction when treated to an acetylcholine (AcCH) concentration of 10 to the 11 power M. The treshold concentration of AcCh for normal rats was 10 to the -5 M. Airways of malnourished rats were also more sensitive to cold. (3) Rehabilitation of the malnourished rats attenuated the response to AcCh. Recovery, however, was not complete. (4) Prior application of phentolamine and atropine markedly reduced the sensitivity of the airways of malnourished rats to AcCh. The results seem to indicate that O-adrenoceptors and the vagus nerve may be involved in the observed increased reactivity of airways of malnourished rats.(AU)

Direct determination of luminal diameter changes in intrapulmonary airways

A method is decribed for the direct measurement of changes in luminal diameter at all levels of the airway. Using this method it was found that (i) abrupt bronchiolar collapse occurred in the preterminal and terminal bronchioles once the luminal diameter was reduced to a critical level: (ii) decreased temperatures resulted in airway narrowing which was reversed by increasing the temperature to above 25 degrees C; as a rule, airway narrowing followed a cranial to caudal direction, and higher concentration of a drug being required to close the peripheral airways; (iii) bronchodilators except Carbuterol had no effect on resting bronchial tone or on acetylcholine-induced constriction in the absence of O-adrenoreceptor blockade; (iv) at 35 degrees C rhythmic waves (frequency 6--20/min) were observed; these waves travelled from the periphery in a cranial direction. (AU)