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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 268 |
| Issue number | 4 37-4 |
| State | Published - 1995 |
| Externally published | Yes |
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Keywords
- birth
- ductus arteriosus
- guanylate cyclase
- nitric oxide
- transitional circulation
- vascular smooth muscle
ASJC Scopus subject areas
- Physiology
- Agricultural and Biological Sciences(all)
Cite this
Disruption of cGMP production in pulmonary arteries isolated from fetal lambs with pulmonary hypertension. / Steinhorn, Robin H; Russell, J. A.; Morin, F. C.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 268, No. 4 37-4, 1995.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Disruption of cGMP production in pulmonary arteries isolated from fetal lambs with pulmonary hypertension
AU - Steinhorn, Robin H
AU - Russell, J. A.
AU - Morin, F. C.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - birth
KW - ductus arteriosus
KW - guanylate cyclase
KW - nitric oxide
KW - transitional circulation
KW - vascular smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=0028948690&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028948690&partnerID=8YFLogxK
M3 - Article
C2 - 7733349
AN - SCOPUS:0028948690
VL - 268
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 4 37-4
ER -