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Blood vessels may release higher than normal amounts of nitric oxide in response to increases in blood flow. Nitric oxide is produced by the body and is known to dilate blood vessels. Researchers used newly delivered placentas to test the effect of increases in blood flow, and found that without adding the nitric oxide inhibitor N-nitro-L-arginine, increased blood flow caused the release of nitric oxide. This finding suggests that increases in blood flow may cause relaxation of blood vessels in the fetus and placenta. Relaxed blood vessels may be desirable in the fetus and placenta when they are affected by diabetes, slow fetal growth, or high blood pressure. Increased blood flow may influence the release of nitric oxide more than increased blood viscosity.

OBJECTIVE: We hypothesized that the endothelial-derived relaxing factor nitric oxide may contribute to low resting vascular tone and may attenuate vasoconstrictor action in the human fetal-placental circulation. STUDY DESIGN: Isolated human placental cotyledons were dually perfused in vitro, and the effects of N-monomethyl-L-arginine and N-nitro-L-arginine (3 x [10.sup.-4] mol/L), which are nonmetabolizable analogs of L-arginine, the substrate for nitric oxide synthase, on resting perfusion pressure and on the fetal-placental circulation preconstricted with U46619 ([10.sup.-8] mol/L) or endothelin-1 ([10.sup.-8] mol/L) were established. Responses before and after inhibition were compared by paired t test. The effects of glyceryl trinitrate ([10.sup.-6] mol/L), acetylcholine ([10.sup.-4] mol/L), the calcium ionophore A23187 ([10.sup.-6] mol/L), and histamine ([10.sup.-8] to [10.sup.-4] mol/L) were also determined in the preconstricted fetal-placental circulation. RESULTS: Both N-monomethyl-L-arginine and N-nitro-L-arginine (3 x [10.sup.-4] mol/L) increased resting perfusion pressure (p < 0.06), and N-nitro-L-arginine promptly and significantly increased perfusion pressure in the fetal-placental circulation preconstricted with U46619 (p < 0.0004) or endothelin-1 (p < 0.06). Nitric oxide generated by addition of glyceryl trinitrate ([10.sup.-6] mol/L) attenuated the vasoconstrictor effects of U46619 (p < 0.026) or endothelin-1 (p < 0.01). Neither acetylcholine nor the calcium ionophore A23187 had an effect on the fetal-placental circulation, whereas bradykinin further increased perfusion pressure. Histamine only relaxed the preconstricted preparations at concentrations ([10.sup.-6] to [10.sup.-4] mol/L) above those shown to release nitric oxide in other systems. CONCLUSION: The stimulus to nitric oxide generation in the fetal-placental circulation may be hydrodynamic. Nitric oxide appears to contribute to maintenance of basal vascular tone and to attenuate the actions of vasoconstrictors in this circulation. (Am J Obstet Gynecol 1992:166:224-30.)

Objective: The purpose of our study was to determine the vasoactivity of calcitonin gene-related peptide (CGRP), parathyroid hormone (PTH), and parathyroid hormon-related protein (PTHrP) in the human fetal-placental circulation in vitro. Methods: Dually perfused placental cotyledons from term pregnancies were used in this study. Results: Calcitonin gene-related peptide, PTHrP (both 10-10–10-6mol/L), and PTH (10-8–10-6mol/L) demonstrated a significant concentration-dependent vasodilator effect (P =.0007, P =.0172, P =.0063, respectively), following preconstnction with a thromboxane mimetic U46619. The CGRP-1 receptor inhibitor CGRP8-37(10-6mol/L) significantly inhibited (P =.0131) the CGRP-induced vasodilator effect, while the nitric oxide synthesis inhibitor n-nitro-l-arginine showed no inhibitory effect. Conclusions: These results demonstrate the vasodilator effects of CGRP, PTH, and PTHrP in the human fetal-placental circulation. Calcitonin gene-related peptide and PTHrP were of equal potency, and both were approximately 100 times more potent than PTH. This study also suggests the CGRP may exert its vasodilator effect through two classes of receptors in the human placenta and may do so independently of nitric oxide. (J Soc Gynecol Invest 1994;1: 19–24)