Biomedical subjects

Michael C Dennedy

Publications and source records attributed to Michael C Dennedy.

4 recordsLinked to original sources

PubMed2004

Cannabinoids and the human uterus during pregnancy.

OBJECTIVE: The aim of this study was to investigate the expression of cannabinoid receptors in human uterine smooth muscle during pregnancy and to evaluate the effects of endogenous and exogenous cannabinoids on myometrial contractility in vitro. STUDY DESIGN: Human myometrial biopsy specimens were obtained at elective cesarean delivery and snap frozen or mounted for isometric recording under physiologic conditions. Cumulative doses of the endogenous cannabinoid anandamide or the exogenous cannabinoid Delta(9) (indicates a double bond between carbons 9 and 10) tetrahydrocannabinol were added in the range 1 nmol/L to 100 micromol/L. Selectivity of the cannabinoid receptor agonists was investigated with specific antagonists for the CB(1) and the CB(2) receptors. Reverse transcription-polymerase chain reaction with primers for the CB(1) and CB(2) receptors was performed on messenger RNA that was isolated from human pregnant myometrium. RESULTS: Both anandamide and Delta(9)-tetrahydrocannabinol exerted a direct relaxant effect on human pregnant myometrium in vitro, which was of equal potency for both compounds. This relaxant effect was antagonized by the specific CB(1) receptor antagonist, SR 141716, but not by the specific CB(2) receptor antagonist, SR 144528 (n=6 specimens, P<.01). Both the CB(1) and CB(2) receptors are expressed in human myometrium. CONCLUSIONS: Both endogenous and exogenous cannabinoids exert a potent and direct relaxant effect on human pregnant myometrium, which is mediated through the CB(1) receptor. This highlights a possible role for endogenous cannabinoids during human parturition and pregnancy. These results also support the view that the use of exogenous cannabinoids during pregnancy is not linked independently with preterm labor.

Adult↗

PubMed2004

Anti-hypertensive therapy and the feto-placental circulation: effects on umbilical artery resistance.

OBJECTIVE: To investigate and compare the direct effects of compounds used in the treatment of hypertensive disease in pregnancy on human umbilical artery resistance in vitro. METHODS: Isometric tension recordings were performed under physiological conditions on human umbilical arterial rings (n=30). The in vitro effects of labetolol, hydralazine, alpha-methyldopa, nifedepine and magnesium sulphate (at concentration ranges from 1 nanomolar to 1 millimolar), and their respective vehicle controls, were measured. Results were expressed as -logEC50 (pD2) and mean maximal inhibition values for each compound. RESULTS: All compounds investigated, except alpha methyldopa, exerted a significant relaxant effect on umbilical arterial tone. Alpha-methyldopa was significantly less potent when compared to all other compounds (mean maximal inhibition value [20.89+/-7.99%] versus all other agents [range 63.15+/-8.70-84.12+/-3.84%] (P<0.01)). The dose response curve of nifedipine yielded a significantly greater PD2 value when compared to that of hydralazine, labetalol, and magnesium sulphate (PD2 value [5.82+/-0.34] versus the above groups [range 3.10+/-0.09-3.52+/-0.14] (P <0.01)). CONCLUSION: These findings demonstrate that agents commonly used for the treatment of hypertensive disease in pregnancy, excluding alpha-methyldopa, have significant direct effects on the feto-placental circulation. These results suggest that alpha-methyldopa administration during pregnancy is less likely to produce significant direct effects on fetal vasculature then other agents used.

Adult↗

PubMed2002

Polyamine effects on human myometrial contractility.

OBJECTIVE: This study was undertaken to investigate the effects of the polyamine spermine on human uterine contractility. STUDY DESIGN: Under physiologic conditions, an isometric tension recording was performed in isolated myometrial strips from biopsy specimens obtained at elective cesarean delivery (n = 24 specimens) and from premenopausal hysterectomy specimens (n = 6 specimens). The effects of spermine (1 micromol/L-10 mmol/L in cumulative doses) on spontaneous, agonist-induced myometrial contractions were measured, and dose response curves were constructed. The pD(2) (-log EC(50)) values and the maximal inhibition values achieved were compared for spontaneous and agonist-induced contractions. RESULTS: Spermine exerted a potent relaxant effect on all spontaneous and agonist-induced myometrial contractions, with mean maximal inhibition values between 62.8% +/- 4.3% and 91.4% +/- 1.8% and pD(2) values between 2.66 +/- 0.23 and 4.01 +/- 0.20. Its inhibitory effect varied significantly with different contraction types (pD(2), P <.05; mean maximal inhibition, P <.001), and it was least potent on BAY K 8644-elicited contractions (pD(2), P <.05; mean maximal inhibition, P <.01). CONCLUSION: The polyamine spermine exerts a potent relaxant effect on human uterine tissue. This effect appears to be mediated, at least partially, by calcium antagonism. Polyamines may play a role in the maintenance of uterine quiescence during pregnancy.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2002

Beta2- and beta3-adrenoreceptor agonists: human myometrial selectivity and effects on umbilical artery tone.

OBJECTIVE: The purpose of this study was to investigate the functional selectivity of the beta(3)-adrenoreceptor agonist BRL 37344 and the beta(2)-adrenoreceptor agonist ritodrine for their putative receptors in human pregnant myometrium in vitro and to examine the possibility that BRL 37344 may exert an effect on other beta-adrenoreceptor subtypes. This study also aimed comparatively to evaluate the in vitro effects of BRL 37344 and ritodrine on human vascular tissue tone. STUDY DESIGN: The effects of BRL 37344 (1 nmol/L-100 micromol/L) and ritodrine (1 nmol/L-100 micromol/L) on isometric tension recordings that were performed in isolated myometrial strips that were obtained at elective cesarean delivery and in human umbilical artery rings that were obtained at term were measured. Antagonism of the effects of BRL 37344 and ritodrine in human myometrial tissue was investigated with the antagonists butoxamine (1 micromol/L), propranolol (1 micromol/L), and bupranolol (1 micromol/L). The concentrations that produced a 50% maximal effect, the mean maximal inhibition that was achieved, and the percentage of contractility that was observed were compared. RESULTS: Bupranolol (n = 6), but not butoxamine (n = 6) or propranolol (n = 6), antagonized the relaxant effects of BRL 37344 in human pregnant myometrium; all three compounds (n = 6, respectively) antagonized the effects of ritodrine. At concentrations of >1 micromol/L, ritodrine exerted a significantly more potent vasodilatory effect than BRL 37344 on human umbilical artery tone (P <.01). CONCLUSION: The relaxant effects of BRL 37344 appear to be mediated solely through the beta(3)-adrenoreceptor agonist, although ritodrine may exert an effect on beta(1)-, beta(2)-, and beta(3)-adrenoreceptor agonists. This and the reduction in vascular tissue effects observed with BRL 37344 suggest that uterine beta(3)-adrenoreceptor modulation may provide a novel scientific approach to tocolysis with fewer vascular adverse effects.

Adrenergic beta-2 Receptor Agonists↗