J Korean Med Sci.  2005 Feb;20(1):13-19. 10.3346/jkms.2005.20.1.13.

Chronic Hypoxia Alters Vasoconstrictive Responses of Femoral Artery in the Fetal Sheep

Affiliations
  • 1Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, Korea. kimyh@chonnam.ac.kr
  • 2Albany Medical College, Albany, New York 12208, U.S.A.
  • 3Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, U.S.A.

Abstract

The purpose of this study was to determine if mild hypoxia alters the responsiveness to vasoactive agents in the renal and the femoral arteries in the fetal sheep. Ten pregnant sheep were operated under halothane anesthesia at 116 to 124 days' gestation. A maternal tracheal catheter was placed for infusing compressed air (control group, n=5) or nitrogen (hypoxia group, n=5) starting on post operative day 6 and maintained for 5 days. Femoral and renal arteries were harvested from the fetus to study the constriction response to phenylephrine (PE 10(-9) to 10(-5) mol/L). To determine the involvement of nitric oxide as a modulator of vessel constriction, N-nitro-Larginine methyl ester (L-NAME) was used at a concentration of 10(-4) mol/L in parallel chambers. In the hypoxia group, maternal Pao2 significantly decreased from a base-line of 110.4 +/-1.4 to 80.5 +/-1.6 (mmHg, p <0.01), fetal Pao2 significantly decreased from a baseline of 20.9 +/-0.3 to 15.5 +/-0.1 (mmHg, p <0.01). Hypoxia was associated with a significant increase in PE maximal response in the absence (184.5 +/-6.6 vs. 146.2 +/-4.3) and presence (166.9 +/-6.3 vs. 145.0 +/-4.5) of L-NAME, and a decrease in EC50 in the absence (6.0 +/-1.1 vs. 27.0 +/-4.1) of L-NAME of femoral arteries. However, there were no significant differences in PE maximal response and EC50 in the absence and presence of L-NAME of renal arteries. We concluded that mild chronic hypoxia seems to increase the fetal femoral artery response to PE, but not in the fetal renal artery. This observation is consistent with a redistribution of cardiac output away from the carcass.

Keyword

Anoxia; Femoral artery; Blood Vessels; Phenylephrine

MeSH Terms

Animals
*Anoxia
Blood Glucose/metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors/pharmacology
Femoral Artery/*embryology/*pathology
Hematocrit
Hydrogen-Ion Concentration
Kidney/blood supply
Lactates/blood/metabolism
NG-Nitroarginine Methyl Ester/pharmacology
Nitric Oxide/metabolism
Nitric-Oxide Synthase/antagonists & inhibitors
Phenylephrine/chemistry/metabolism/pharmacology
Renal Artery/pathology
Sheep/*embryology
Time Factors
Vasoconstrictor Agents/*pharmacology

Figure

  • Fig. 1 Concentration-effect curves for phenylephrine (PE 10-9 to 10-5 mol/L) in isolated fetal sheep renal and femoral arteries obtained from normoxic (control group n=5) and hypoxic fetuses (hypoxia group n=5). Arteries were studied with and without L-NAME in the bath. Results are expressed as a percentage of the maximal response to KCl in each vessel and presented as mean±SEM.


Reference

1. Rudolph AM, Heymann MA. Circulatory changes during growth in the fetal lamb. Circ Res. 1970. 26:289–299.
Article
2. Campbell AG, Dawes GS, Fishman AP, Hyman AI. Regional redistribution of blood flow in the mature fetal lamb. Circ Res. 1967. 21:229–235.
Article
3. Cohn HE, Sacks EJ, Heymann MA, Rudolph AM. Cardiovascular responses to hypoxemia and acidemia in fetal lambs. Am J Obstet Gynecol. 1974. 120:817–824.
Article
4. Gleed RD, Poore ER, Figueroa JP, Nathanielsz PW. Modification of maternal and fetal oxygenation with the use of tracheal gas infusion. Am J Obstet Gynecol. 1986. 155:429–435.
Article
5. Nathanielsz PW, Abel MH, Bass FG, Krane EJ, Thomas AL, Liggins GC. Pituitary stalk-section and some of its effects on endocrine function in the fetal lamb. Q J Exp Physiol Cogn Med Sci. 1978. 63:211–219.
Article
6. Towell ME, Figueroa J, Markowitz S, Elias B, Nathanielsz P. The effect of mild hypoxemia maintained for twenty-four hours on maternal and fetal glucose, lactate, cortisol, and arginine vasopressin in pregnant sheep at 122 to 139 days' gestation. Am J Obstet Gynecol. 1987. 157:1550–1557.
Article
7. Jensen A, Berger R. Fetal circulatory responses to oxygen lack. J Dev Physiol. 1991. 16:181–207.
8. Kruger H, Arias-Stella J. The placenta and the newborn infant at high altitudes. Am J Obstet Gynecol. 1970. 106:586–591.
9. Mazess RB. Neonatal mortality and altitude in Peru. Am J Phys Anthropol. 1965. 23:209–214.
Article
10. McCullough RE, Reeves JT, Liljegren RL. Fetal growth retardation and increased infant mortality at high altitude. Obstet Gynecol Surg. 1977. 32:596–598.
Article
11. McQuillan LP, Leung GK, Marsden PA, Kostyk SK, Kourembanas S. Hypoxia inhibits expression of eNOS via transcriptional and post-transcriptional mechanism. Am J Physiol. 1994. 267:H1921–H1927.
12. Arnet UA, McMillan A, Dinerman JL, Ballermann B, Lowenstein CJ. Regulation of endothelial nitric-oxide synthase during hypoxia. J Biol Chem. 1996. 271:15069–15073.
Article
13. Moncada S, Rees DD, Schulz R, Palmer RM. Development and mechanism of specific supersensitivity to nitrovasodilators after inhibition of vascular nitric oxide synthesis in vivo. Proc Natl Acad Sci USA. 1991. 88:2166–2170.
14. Thompson LP, Weiner CP. Effects of acute and chronic hypoxia on nitric oxide-mediated relaxation of fetal guinea pig arteries. Am J Obstet Gynecol. 1999. 181:105–111.
Article
15. Millard RW, Baig H, Vatner SF. Prostaglandin control of the renal circulation in response to hypoxemia in the fetal lamb in utero. Circ Res. 1979. 45:172–179.
Article
16. Elton TS, Oparil S, Taylor GR, Hicks PH, Yang RH, Jin H, Chen YF. Normobaric hypoxia stimulates endothelin-1 gene expression in the rat. Am J Physiol. 1992. 263:R1260–R1264.
Article
17. Doyle MP, Walker BR. Attenuation of systemic vasoreactivity in chronically hypoxic rats. Am J Physiol. 1991. 260:R1114–R1122.
18. Aoki VS, Robinson SM. Hindquarters vascular responses in chronically hypoxic rats. Am J Physiol. 1969. 217:661–665.
Article
19. Jin H, Yang RH, Chen YF, Thornton RM, Jackson RM, Oparil S. Hemodynamic effects of arginine vasopressin in rats adapted to chronic hypoxia. J Appl Physiol. 1989. 66:151–160.
Article
20. Fukuda S, Morioka M, Tanaka T, Taga K, Shimoji K. Endothelium dependence of effects of high PCO2 on agonist-induced contractility of rat aorta. Am J Physiol. 1993. 264:H512–H519.
21. White MM, McCullough RE, Dyckes R, Robertson AD, Moore LG. Effects of pregnancy and chronic hypoxia on contractile responsiveness to alpha 1 adrenergic stimulation. J Appl Physiol. 1998. 85:2322–2329.
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