endothelin-1 and 1-4-dihydropyridine

To evaluate factors contributing to both placental hypoperfusion and maternal vasoconstriction in pre-eclampsia.. Single centre, comparative study of calcium-channel density and affinity in the placental bed of pregnant women with normotension and pre-eclampsia.. Teaching hospital.. Twenty-two primigravidae in the third trimester of pregnancy: 10 with pre-eclampsia and 12 normotensive.. Plasma levels of endothelin-1 (by RIA) and noradrenaline (by HPLC-ED) were measured. Both pharmacological characterisation and anatomical localisation of dihydropyridine-sensitive binding sites (using radioligand-binding studies and autorradiographic techniques) were determined with 3H-isradipine in placental bed tissues to determine both the density (Bmax) and the affinity (Kd) of receptor sites.. Higher plasma levels of endothelin-1 and noradrenalin were found in women with pre-eclampsia compared with normotensive women. Placental bed tissues bound 3H-isradipine in a saturable, reversible time and temperature-dependent manner with very low Kd values. Study of the 3H-isradipine specificity binding included the use of several dihydropyridine displacers. In the group with pre-eclampsia the Scatchard analysis of the results showed a significant increase (P < 0.001) both in the affinity [Kd = 0.23 nmol (0.04) vs 0.45 nmol (0.03), pre-eclampsia vs normotensive] and in the density of calcium-channel binding sites [Bmax = 77.70 fmol/mg (1.30) vs 64.30 fmol/mg (1 80) tissue, pre-eclampsia vs normotensive]. Autoradiography confirmed that in the placental bed tissue of those with pre-eclampsia there was a much higher silver grain density in the arteries walls, compared with normotensive women.. In pre-eclampsia there is an increase in the maternal circulation of two strong vasoconstrictor factors (endothelin-1 and noradrenalin) and a sharp increase both in the density and the affinity of calcium-channel binding sites in placental bed central area. The latter may strongly contribute to the perpetuation of the uteroplacental hypoperfusion either by itself or by amplifying the local actions of circulating factors, such as endothelin-1 and noradrenalin.

Topics: Adult; Autoradiography; Binding Sites; Calcium Channel Blockers; Calcium Channels; Dihydropyridines; Endothelin-1; Female; Humans; Norepinephrine; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

Progesterone, prostaglandin and follicular fluid are reported to enhance the acrosome reaction through the influx of extracellular calcium into the cytoplasm of human spermatozoa. Prostaglandins are present within the male reproductive tract, and high concentrations of prostaglandins exist in seminal fluid. In order to investigate the mechanisms by which prostaglandins enhance the acrosome reaction through calcium influx, the intracellular calcium response induced by progesterone, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) and follicular fluid was measured using fura-2. PGE1 and PGE2 promoted calcium influx dose dependently through dihydropyridine insensitive calcium channels. Refractoriness of the elevation of intracellular Ca2+ concentration ([Ca2+]i) to a second stimulus occurred when 60 microg/ml PGE1 was administered 100 s after the prior administration of 60 microg/ml of PGE1, and similarly when 1 microg/ml of progesterone was administered 100 s after the prior administration of 1 microg/ml of progesterone. Refractoriness also occurred when 60 microg/ml PGE1 was administered after the prior addition of 60 microg/ml PGE2, but did not occur between PGE1 and progesterone. Pertussis toxin (PTX) did not modify the changes in [Ca2+]i after the addition of PGE1 or PGE2. In conclusion, PGE1 and PGE2 promoted calcium influx through PTX-insensitive calcium channels which appeared to be recognized by a common receptor different from that of progesterone.

Topics: Acrosome; Adult; Alprostadil; Angiotensin II; Atrial Natriuretic Factor; Body Fluids; Calcium; Calcium Channel Blockers; Calcium Channels; Culture Media; Cyclic AMP; Dihydropyridines; Dinoprost; Dinoprostone; Drug Interactions; Endothelin-1; Female; Humans; Infertility, Male; Ion Transport; Male; Ovarian Follicle; Pentoxifylline; Pertussis Toxin; Progesterone; Sperm Capacitation; Sperm-Ovum Interactions; Spermatozoa; Virulence Factors, Bordetella