Disruption of cGMP production in pulmonary arteries isolated from fetal lambs with pulmonary hypertension

Robin H Steinhorn, J. A. Russell, F. C. Morin

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Ligation of the ductus arteriosus of the fetal sheep produces severe pulmonary hypertension at birth. Standard tissue bath techniques were used to study third- and fourth-generation pulmonary arteries and veins isolated from fetal sheep with pulmonary hypertension created by ligation of the ductus arteriosus 11-12 days before birth as well as from age-matched control sheep. Vessels pretreated with indomethacin and propranolol were submaximally preconstricted with norepinephrine before exposure to A-23187 (10-8 to 3 x 10-7 M), sodium nitroprusside (SNP; 10-9 to 10-5 M), and nitric oxide (NO) gas (1-973 ppm). Pulmonary veins in both control and ligated animals relaxed similarly and completely to A-23187, SNP, and NO. Control pulmonary arteries relaxed by 16 ± 2% to A-23187 and relaxed completely to SNP and NO, with concentration-response curves shifted rightward of those observed in pulmonary veins. Pulmonary arteries from ligated animals did not relax at all to A-23187. SNP relaxations in ligated arteries were shifted rightward of control. Ligated arteries relaxed by only 11 ± 5% to the highest dose of NO. However, control and ligated pulmonary arteries relaxed similarly to 8- bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP; 10-5 to 10-3 M) and atrial natriuretic peptide (10-9 to 10-7 M). These data are most simply explained by decreased arterial vascular smooth muscle sensitivity to NO at the level of soluble guanylate cyclase.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume268
Issue number4 37-4
StatePublished - 1995
Externally publishedYes

Keywords

  • birth
  • ductus arteriosus
  • guanylate cyclase
  • nitric oxide
  • transitional circulation
  • vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Agricultural and Biological Sciences(all)

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