This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bustamante, S. A. Articles by Miller, M. J.S. Search for Related Content PubMed PubMed Citation Articles by Bustamante, S. A. Articles by Miller, M. J.S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE

(Circulation. 1996;94:1948-1953.)
© 1996 American Heart Association, Inc.

Articles

Inducible Nitric Oxide Synthase and the Regulation of Central Vessel Caliber in the Fetal Rat

Sergio A. Bustamante, MD; Ying Pang, MD; Silvia Romero, MD; Maria R. Pierce, MD; Cynthia A. Voelker, MD; Jane H. Thompson, BS; Manuel Sandoval, PhD; Xiaoping Liu, PhD; Mark J.S. Miller, PhD

the Departments of Pediatrics of Louisiana State University Medical Center and Tulane University Medical Center (M.R.P), New Orleans, La.

Correspondence to Mark J.S. Miller, PhD, Department of Pediatrics, LSU Medical Center, 1542 Tulane Ave, New Orleans, LA 70112.

Background The purpose of this study was to evaluate the possibility that inducible nitric oxide synthase (iNOS) regulates the fetal circulation.

Methods and Results Positive evidence for iNOS gene expression was noted in heart central vessels and placenta of untreated rat fetuses. Rats in the last week of pregnancy were treated for 5 days with L-N^G-(1-Iminoethyl)lysine (L-NIL), a selective inhibitor of iNOS, at 1, 10, and 100 µg/mL in the drinking water. To raise NO levels, lipopolysaccharide (LPS) 30 µg/kg was given by intraperitoneal injection, and sodium nitroprusside (SNP) was placed in mini-osmotic pumps to deliver 10 µg/kg per minute. Control animals were undisturbed. On day 21 of gestation, dams were anesthetized and fetuses were delivered by cesarean section and rapidly frozen in isopentane chilled in liquid nitrogen. Frozen sections (10 µm) were used to reconstruct a computer-generated three-dimensional image of the great vessels and ductus arteriosus. Significant constriction of the great vessels and ductus arteriosus was observed with L-NIL, whereas both LPS and SNP dilated these vessels. The vasorelaxant effect of LPS was blocked by L-NIL. NO release from placental explants was 633±41 nmol/L under basal conditions, increasing to 4.0±0.4 µmol/L with LPS administration, although placental iNOS message and protein levels were unchanged.

Conclusions We suggest that nitric oxide, generated by iNOS, plays a significant role in control of major vessel and ductus arteriosus caliber in the rat fetus. In regard to the nitrergic regulation of the circulation, the fetus is clearly different from the adult.

Key Words: ductus arteriosus, patent • free radicals • pharmacology • polymerase chain reaction • vasculature

This article has been cited by other articles:

				C. Richard, J. Gao, B. LaFleur, B. W. Christman, J. Anderson, N. Brown, and J. Reese Patency of the preterm fetal ductus arteriosus is regulated by endothelial nitric oxide synthase and is independent of vasa vasorum in the mouse Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2004; 287(3): R652 - R660. [Abstract] [Full Text] [PDF]

				M. J. Morin, S. M. Karr, R. A. Faris, and P. A. Gruppuso Developmental variability in expression and regulation of inducible nitric oxide synthase in rat intestine Am J Physiol Gastrointest Liver Physiol, August 1, 2001; 281(2): G552 - G559. [Abstract] [Full Text] [PDF]

				F. Coceani, Y.-A. Liu, E. Seidlitz, L. Kelsey, T. Kuwaki, C. Ackerley, and M. Yanagisawa Endothelin A receptor is necessary for O2 constriction but not closure of ductus arteriosus Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1521 - H1531. [Abstract] [Full Text] [PDF]

				M. J. S. Miller and M. Sandoval III. A molecular prelude to intestinal inflammation Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G795 - G799. [Abstract] [Full Text] [PDF]

				M. A. Anwar, M. Schwab, L. Poston, and P. W. Nathanielsz Betamethasone-mediated vascular dysfunction and changes in hematological profile in the ovine fetus Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1137 - H1143. [Abstract] [Full Text] [PDF]

				R. L. Rairigh, L. Storme, T. A. Parker, T. D. le Cras, J. P. Kinsella, M. Jakkula, and S. H. Abman Inducible NO synthase inhibition attenuates shear stress-induced pulmonary vasodilation in the ovine fetus Am J Physiol Lung Cell Mol Physiol, March 1, 1999; 276(3): L513 - L521. [Abstract] [Full Text] [PDF]

				J. J. Smolich NO modulates fetoplacental blood flow distribution and whole body oxygen extraction in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1998; 274(5): R1331 - R1337. [Abstract] [Full Text] [PDF]

				G. C. S. Smith The Pharmacology of the Ductus Arteriosus Pharmacol. Rev., March 1, 1998; 50(1): 35 - 58. [Abstract] [Full Text] [PDF]

				M. Challah, S. Nadaud, M. Philippe, T. Battle, F. Soubrier, B. Corman, and J. B. Michel Circulating and cellular markers of endothelial dysfunction with aging in rats Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1941 - H1948. [Abstract] [Full Text] [PDF]

				T. Takizawa, H. Yoshikawa, M. Yamada, and H. Morita Expression of nitric oxide synthase isoforms and detection of nitric oxide in rat placenta Am J Physiol Cell Physiol, April 1, 2002; 282(4): C762 - C767. [Abstract] [Full Text] [PDF]

				R. L. Rairigh, T. A. Parker, D. D. Ivy, J. P. Kinsella, I-D. Fan, and S. H. Abman Role of Inducible Nitric Oxide Synthase in the Pulmonary Vascular Response to Birth-Related Stimuli in the Ovine Fetus Circ. Res., April 13, 2001; 88(7): 721 - 726. [Abstract] [Full Text] [PDF]