ROLE OF EXTRACELLULAR CALCIUM AND CALCIUM CHANNELS IN THE RESPONSE OFHUMAN PLACENTAL VENOUS SMOOTH-MUSCLE TO ENDOTHELIN-1

OBJECTIVE: Our purpose was to evaluate the role of calcium and calcium channels in endothelin-1-induced contraction of the smooth muscle of human placental veins. STUDY DESIGN: Placentas were collected after va ginal delivery at term. After their removal from the chorionic plate, placental veins were divided into rings that were suspended in organ c hambers and stretched to optimal tension. In the first part of the stu dy, vessels from six women were initially suspended in calcium-poor mo dified Krebs-Ringer solution. They were then treated with either EGTA [ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid; calcium chelator, 0.5 mmol/L] or calcium chloride 2.5 mmol/L (control ). Endothelin-1 was then added cumulatively (10(-10) to 10(-7) mol/L), and the resulting changes in isometric tensions were recorded. In the second part of the study vessels from six other women were treated wi th either (1) normal modified Krebs-Ringers solution (control), (2) ca lcium-poor modified Krebs-Ringers solution, or (3) nicardipine (dihydr opyridine calcium channel inhibitor, 10(-7) mol/L) in separate organ c hambers. Endothelin-1 was then added cumulatively. RESULTS: Endothelin -1 produced concentration-dependent contractions in placental veins, w ith maximal tension reached at 10(-7) mol/L. Substitution of calcium-p oor for standard Krebs-Ringers solution in the organ chamber abolished contractions to low endothelin-1 concentrations (less-than-or-equal-t o 10(-8) mol/L, p < 0.001) but did not affect the contractile response to higher concentrations. EGTA abolished contractions to all concentr ations tested (p < 0.02). Nicardipine significantly, but incompletely, inhibited the contractile responses to all endothelin-1 concentration s tested (p < 0.05). CONCLUSIONS: Endothelin-1 induces contraction of the smooth muscle of human placental veins, which requires the influx of extracellular calcium. Dihydropyridine-sensitive calcium channels r epresent a major route of entry, but other pathways participate. The f etal effects of nifedipine and other calcium-channel blockers deserve specific evaluation in intrauterine growth retardation and other pregn ancies complicated by elevated fetal levels of endothelin-1.