Effects of amitriptyline, a tricyclic antidepressant, on smooth muscle reactivity in isolated rat trachea.

PURPOSE: This study was designed to investigate the action of amitriptyline, a tricyclic antidepressant, on airway smooth muscle reactivity and its underlying mechanisms. METHODS: In isolated rat trachea, isometric force was recorded to examine the effects of amitriptyline on the contractile response to acetylcholine (ACh), electrical field stimulation (EFS), calyculin A (a myosin light chain phosphatase inhibitor), and sphingosylphosphorylcholine (SPC; a Rhokinase activator). In addition, inositol monophosphate (IP1) accumulation was measured to examine its effects on inositol 1, 4, 5-trisphosphate (IP(3)) production during stimulation with ACh. RESULTS: Amitriptyline inhibited the contractile responses to ACh, EFS, calyculin A, and SPC, with the concentrations of amitriptyline (mean +/- SD) required to exert 50% inhibition (IC(50)) being 4.3 +/- 1.3 microM, 3.2 +/- 1.6 microM, 256.4 +/- 106.4 microM, and 98.2 +/- 21.8 microM, respectively. In addition, amitriptyline (10 microM) eliminated the ACh (10 microM)-induced IP(1) accumulation. CONCLUSION: The results suggest that amitriptyline does not influence tracheal smooth muscle reactivity at clinical concentrations ( or =1 microM). The attenuated response to ACh brought about by amitriptyline is presumably due, at least in part, to the inhibition of phosphatidylinositol (PI) metabolism. The ability of amitriptyline to inhibit the calyculin Ainduced contraction suggests that amitriptyline also inhibits the Ca(2+)-calmodulin-myosin light chain pathway independently of the inhibition of PI metabolism. Finally, the difference between the IC(50) values for SPC-induced contraction and those for calyculin A-induced contraction suggests that amitriptyline may also inhibit the Rho-kinase pathway

Marital status and suicide in the National Longitudinal Mortality Study

OBJECTIVES—The purpose of the study was to examine the effect of marital status on the risk of suicide, using a large nationally representative sample. A related objective was to investigate the association between marital status and suicide by sex.
METHODS—Cox proportional hazards regression models were applied to data from the National Longitudinal Mortality Study, based on the 1979-1989 follow up. In estimating the effect of marital status, adjustments were made for age, sex, race, education, family income, and region of residence.
RESULTS—For the entire sample, higher risks of suicide were found in divorced than in married persons. Divorced and separated persons were over twice as likely to commit suicide as married persons (RR=2.08, 95% confidence intervals (95% CI) 1.58, 2.72). Being single or widowed had no significant effect on suicide risk. When data were stratified by sex, it was observed that the risk of suicide among divorced men was over twice that of married men (RR=2.38, CI 1.77, 3.20). Among women, however, there were no statistically significant differentials in the risk of suicide by marital status categories.
CONCLUSIONS—Marital status, especially divorce, has strong net effect on mortality from suicide, but only among men. The study showed that in epidemiological research on suicide, more accurate results would be obtained if samples are stratified on the basis of key demographic or social characteristics. The study further observed that failure to control for relevant socioeconomic variables or combining men and women in the same models could produce misleading results.


Keywords: suicide; marital status; socioeconomic status; effect modificatio