Role of neuronal nitric oxide synthase in regulation of vascular and ductus arteriosus tone in the ovine fetus
| Autor: | M. Jakkula, Laurent Storme, T. D. Le Cras, Robyn L. Rairigh, Thomas A. Parker, Neil E. Markham, Steven H. Abman |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Pulmonary Circulation Indazoles Physiology Blotting Western Vasodilation Gestational Age Nitric Oxide Synthase Type I Nitroarginine Nitric oxide chemistry.chemical_compound Fetus Physiology (medical) Internal medicine Medicine Animals Enzyme Inhibitors Sheep biology business.industry Hemodynamics Cell Biology Anatomy Ductus Arteriosus medicine.disease Pulmonary hypertension Acetylcholine Nitric oxide synthase Vasomotor System Endocrinology medicine.anatomical_structure chemistry Circulatory system Vascular resistance biology.protein Nitric Oxide Synthase business Blood vessel |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 278(1) |
| ISSN: | 1040-0605 |
| Popis: | Nitric oxide (NO) is produced by NO synthase (NOS) and contributes to the regulation of vascular tone in the perinatal lung. Although the neuronal or type I NOS (NOS I) isoform has been identified in the fetal lung, it is not known whether NO produced by the NOS I isoform plays a role in fetal pulmonary vasoregulation. To study the potential contribution of NOS I in the regulation of basal fetal pulmonary vascular resistance (PVR), we studied the hemodynamic effects of a selective NOS I antagonist, 7-nitroindazole (7-NINA), and a nonselective NOS antagonist, N-nitro-l-arginine (l-NNA), in chronically prepared fetal lambs (mean age 128 ± 3 days, term 147 days). Brief intrapulmonary infusions of 7-NINA (1 mg) increased basal PVR by 37% ( P < 0.05). The maximum increase in PVR occurred within 20 min after infusion, and PVR remained elevated for up to 60 min. Treatment with 7-NINA also increased the pressure gradient between the pulmonary artery and aorta, suggesting constriction of the ductus arteriosus (DA). To test whether 7-NINA treatment selectively inhibits the NOS I isoform, we studied the effects of 7-NINA andl-NNA on acetylcholine-induced pulmonary vasodilation. The vasodilator response to acetylcholine remained intact after treatment with 7-NINA but was completely inhibited after l-NNA, suggesting minimal effects on endothelial or type III NOS after 7-NINA infusion. Western blot analysis detected NOS I protein in the fetal lung and great vessels including the DA. NOS I protein was detected in intact and endothelium-denuded vessels, suggesting that NOS I is present in the medial or adventitial layer. We conclude that 7-NINA, a selective NOS I antagonist, increases basal PVR, systemic arterial pressure, and DA tone in the late-gestation fetus and that NOS I protein is present in the fetal lung and great vessels. We speculate that NOS I may contribute to NO production in the regulation of basal vascular tone in the pulmonary and systemic circulations and the DA. |
| Databáze: | OpenAIRE |
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