Altered endothelium-dependent relaxations in lambs with high pulmonary blood flow and pulmonary hypertension

Robin H. Steinhorn, James A. Russell, Satyan Lakshminrusimha, Sylvia F. Gugino, Stephen M. Black, Jeffrey R. Fineman

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Congenital heart disease associated with increased pulmonary blood flow produces pulmonary hypertension. To characterize vascular alterations in the nitric oxide (NO)-cGMP cascade induced by increased pulmonary blood flow and pulmonary hypertension, 10 fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt). When the lambs were 4-6 wk of age, we assessed responses of pulmonary arteries (PAs) and pulmonary veins (PVs) isolated from lungs of control and shunted lambs. PVs from control and shunted lambs relaxed similarly to exogenous NO (S-nitrosyl-acetyl-penicillamine), to NO produced endogenously (zaprinast and A-23187), and to cGMP (atrial natriuretic peptide). In contrast, relaxations to A-23187 and zaprinast were blunted in PAs isolated from shunted lambs relative to controls. Inhibitors of NO synthase (NOS) and soluble guanylate cyclase constricted control but not shunt PAs, indicating reduced basal NOS activity in shunt PAs. Pretreatment of shunt PAs with the substrates L-arginine and sepiapterin, a precursor for tetrahydrobiopterin synthesis, did not augment A-23187 relaxations. However, pretreatment with superoxide dismutase and catalase significantly enhanced A-23187 relaxations in shunt PAs. We conclude that increased pulmonary blood flow induces an impairment of endothelium-dependent relaxation that is selective to PAs. The impaired relaxation may be mediated in part by excess superoxide production.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number1 49-1
StatePublished - Jun 12 2001

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Pulmonary Hypertension
Pulmonary Artery
Endothelium
Calcimycin
Lung
Nitric Oxide
Pulmonary Veins
Nitric Oxide Synthase
Blood Vessels
Penicillamine
Atrial Natriuretic Factor
Superoxides
Catalase
Superoxide Dismutase
Arginine
Heart Diseases
Transplants

Keywords

  • Artery
  • Circulation
  • Endothelial nitric oxide synthase
  • Superoxide

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Steinhorn, R. H., Russell, J. A., Lakshminrusimha, S., Gugino, S. F., Black, S. M., & Fineman, J. R. (2001). Altered endothelium-dependent relaxations in lambs with high pulmonary blood flow and pulmonary hypertension. American Journal of Physiology - Heart and Circulatory Physiology, 280(1 49-1).

Altered endothelium-dependent relaxations in lambs with high pulmonary blood flow and pulmonary hypertension. / Steinhorn, Robin H.; Russell, James A.; Lakshminrusimha, Satyan; Gugino, Sylvia F.; Black, Stephen M.; Fineman, Jeffrey R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 280, No. 1 49-1, 12.06.2001.

Research output: Contribution to journalArticle

Steinhorn, RH, Russell, JA, Lakshminrusimha, S, Gugino, SF, Black, SM & Fineman, JR 2001, 'Altered endothelium-dependent relaxations in lambs with high pulmonary blood flow and pulmonary hypertension', American Journal of Physiology - Heart and Circulatory Physiology, vol. 280, no. 1 49-1.
Steinhorn, Robin H. ; Russell, James A. ; Lakshminrusimha, Satyan ; Gugino, Sylvia F. ; Black, Stephen M. ; Fineman, Jeffrey R. / Altered endothelium-dependent relaxations in lambs with high pulmonary blood flow and pulmonary hypertension. In: American Journal of Physiology - Heart and Circulatory Physiology. 2001 ; Vol. 280, No. 1 49-1.
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