Action of histamine on the rapidly adapting airway receptors in the dog

1989 ◽  
Vol 67 (12) ◽  
pp. 1499-1505 ◽  
Author(s):  
K. Ravi ◽  
K. K. Teo ◽  
C. T. Kappagoda

The effects of histamine on the activity of rapidly adapting receptors (RAR) of the airways were investigated in anesthetized dogs. With bolus injections given into the right atrium, the threshold dose of histamine required for the excitation of RAR (n = 7) was 0.82 μg/kg (+1.33/−0.51, geometric mean). With increasing doses of histamine, a dose–response relationship was seen in the activity of RAR. Obstruction of the lymphatic drainage from the lungs reduced the threshold dose to histamine (i.e., shifted the dose–response curve to the left significantly). This change in the dose–response relationship was not accompanied by a corresponding change in the relationship of histamine dose to airway pressures recorded before and after lymphatic obstruction. Against a background of pulmonary venous congestion produced by partial obstruction of the mitral valve, subthreshold doses of histamine stimulated the RAR (n = 4). The excitatory effect of histamine on RAR was found to be abolished by the administration of the H1 receptor antagonist diphenhydramine but not by the H2 receptor antagonist cimetidine. Intravenous infusion of histamine (0.4 μg∙kg−1∙min−1) for a period of 10 min increased the RAR activity (n = 6) significantly without producing detectable changes in airway mechanics. The results indicate that contraction of the smooth muscle of the airways may not be a prerequisite for the excitation of RAR, especially at low doses. It is suggested that some of the effects of histamine on RAR are mediated by a local expansion of the extravascular fluid caused by an increase in the permeability of the bronchial vasculature.Key words: histamine, pulmonary congestion, vagal sensory receptors.

1992 ◽  
Vol 73 (5) ◽  
pp. 2054-2061 ◽  
Author(s):  
T. J. McMahon ◽  
A. D. Kaye ◽  
J. S. Hood ◽  
R. K. Minkes ◽  
B. D. Nossaman ◽  
...  

The effects of the non-peptide antagonist DuP 753 and its metabolite EXP3174 on responses to angiotensin II were investigated in the pulmonary vascular bed of the intact-chest cat. Under conditions of controlled blood flow and constant left atrial pressure, injections of angiotensin II into the perfused lobar artery caused dose-related increases in lobar arterial pressure. Responses to angiotensin II were reproducible and were not changed by meclofenamate or prazosin, indicating that prostaglandin or norepinephrine release does not mediate or modulate pulmonary vascular responses to the peptide. DuP 753 (1–5 mg/kg iv) decreased responses to angiotensin II in a competitive manner, and the duration of the blockade was related to dose of the antagonist. DuP 753 had no significant effect on responses to U-46619, norepinephrine, serotonin, endothelin-1, vasopressin, or BAY K 8644. EXP3174 also decreased responses to angiotensin II without altering responses to agents that act by a variety of mechanisms. The inhibitory effect of EXP3174 (1 mg/kg iv) was not overcome by angiotensin II in the range of doses studied, and the shift to the right of the dose-response curve was nonparallel, suggesting that the blockade was noncompetitive. The blockade was long in duration, and, when the dose of EXP3174 was decreased to 0.1 mg/kg iv, the blockade was surmounted and the shift to the right of the dose-response relationship was parallel. DuP 753 and EXP3174 had little effect on mean baseline pressures in the cat.(ABSTRACT TRUNCATED AT 250 WORDS)


1979 ◽  
Vol 90 (3) ◽  
pp. 394-402 ◽  
Author(s):  
A. Römmler ◽  
C. Viebahn ◽  
U. Schwartz ◽  
J. Hammerstein

ABSTRACT The effects of two consecutive LH-RH injections at 120 min intervals with either a varying first or second LH-RH dose on pituitary gonadotrophin response were investigated in 15 eugonadal women to study pituitary secretory processes. Each volunteer underwent a total of 4 LH-RH double stimulation tests. In group I (n = 8) the first LH-RH dose of each of the 4 tests was fixed at 25 μg, whereas the second LH-RH dose consisted of either 6, 25, 100 or 400 μg. In group II (n= 7) the first LH-RH dose varied between 6 and 400 μg, while the second LH-RH dose was kept constant at 25 μg. Serum gonadotrophin and serum ovarian steroid levels were determined by radioimmunoassay before and after LH-RH administration. The volunteers in both groups served as their own controls. A linear log-dose response relationship was found between the various doses of LH-RH injected and the corresponding LH and FSH elevations elicited. However, the dose of the first LH-RH injection also significantly influenced the gonadotrophin reaction after the second LH-RH injection in a linear log-dose response relationship. Serum levels of oestradiol, 17-hydroxyprogesterone and progesterone significantly increased in response to the elevated serum gonadotrophin levels after LH-RH stimulation during the 4 h test period, but the rise did not correlate to the LH-RH dose used. The results indicate that LH-releasing hormone stimulates not only the release, but also the synthesis of LH and FSH in a dose-related manner. These findings are consistent with our previously reported concept that the magnitude of LH and FSH response to the first LH-RH injection reflects the "storage capacity", while the increase observed after the second LH-RH injection represents the "synthesis capacity" of the gonadotrophs.


1962 ◽  
Vol 41 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Ralph I. Dorfman

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.


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