Related Experiment Video
Updated: Oct 4, 2026

Videomorphometric Analysis of Hypoxic Pulmonary Vasoconstriction of Intra-pulmonary Arteries Using Murine Precision Cut Lung Slices
Published on: January 14, 2014
Pulmonary artery vasoconstriction but not [Ca2+]i signal stimulated by thromboxane A2 is partially resistant to NO
F Pérez-Vizcaíno1, A L Cogolludo, M Ibarra
1Department of Pharmacology, Institute of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain. fperez@eucmax.sim.ucm.es
Abstract:
To characterize the thromboxane A2 (TXA2) -induced resistance to the vasodilator effects of the nitric oxide (NO)/cGMP pathway in pulmonary arteries, we have studied the effects of the NO donor sodium nitroprusside on intracellular calcium concentration ([Ca2+]i) and contractile force recorded simultaneously in isolated piglet pulmonary arteries loaded with fura-2 and contracted with norepinephrine or the TXA2 mimetic U46619 and by activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate. In the TXA2 mimetic- and phorbol 12-myristate 13-acetate plus norepinephrine-stimulated arteries, nitroprusside exhibited lower vasodilator efficacy (and lower potency in the TXA2 mimetic-stimulated arteries) but similar reductions in [Ca2+]i compared with arteries activated by norepinephrine. The nonselective serine/threonine kinase inhibitor staurosporine, but not the selective inhibitor of PKC bisindolylmaleimide, potentiated the relaxation of nitroprusside in the TXA2 mimetic-stimulated arteries. In conclusion, the resistance to NO/cGMP-induced vasodilation in arteries stimulated by TXA2 and PKC involves a reduced ability of the Ca2+-independent mechanisms for smooth muscle vasodilation. The resistance to NO in arteries stimulated by TXA2 is sensitive to staurosporine but not to bisindolylmaleimide, suggesting the involvement of an activation of a serine/threonine kinase distinct from PKC.
Related Concept Videos
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Antihypertensive Drugs: Action of Calcium Channel Blockers
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
Nitric Oxide Signaling Pathway
Pulmonary Hypertension: Classification and Pathogenesis
There are various classifications for PH, each relating to different underlying causes and also...

