RhoA/Rho kinase and nitric oxide modulate the agonist-induced pulmonary artery diameter response time

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 282; no. 3; p. H990
• Main Authors: Boer, Christa, van der Linden, Peter J W, Scheffer, Gert Jan, Westerhof, Nico, de Lange, Jaap J, Sipkema, Pieter
• Format: Journal Article
• Language: English
• Published: United States 01-03-2002
• Subjects: Acetylcholine - pharmacology; Amides - pharmacology; Animals; Electrophysiology - methods; Endothelium, Vascular - physiology; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Lysophospholipids - pharmacology; Male; Microelectrodes; Muscle, Smooth, Vascular - physiology; Nitric Oxide - physiology; Nitroarginine - pharmacology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - physiology; Pulmonary Artery - physiology; Pyridines - pharmacology; Rats; Rats, Wistar; Renal Artery - physiology; rho-Associated Kinases; Sensitivity and Specificity; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0363-6135
• DOI: 10.1152/ajpheart.00093.2001

We studied the amplitude and response time (RT; time to 50% of maximal response) of pulmonary vasoreactivity and investigated whether the characteristics of pulmonary vasoreactivity could be modulated by endothelium removal, nitric oxide (NO) synthase inhibition [N(G)-nitro-L-arginine (L-NNA)], RhoA activation [lysophosphatidic acid (LPA)] and Rho kinase inhibition (Y-27632). Slow acetylcholine-induced pulmonary vasodilation (262 +/- 5 s) was not due to the RT of endothelial NO release (45-55 s) and was always longer than RT in renal arteries (15 +/- 4 s). The rate-determining step is located in the smooth muscle cells. This was confirmed by the existing differences between the RT of the NO solution and KCl-induced renal and pulmonary vasoreactivity in endothelium-denuded arteries. We found that the pulmonary contractile amplitude increases and the RT decreases by L-NNA or LPA. In contrast, Y-27632 reduced the contractile amplitude and increased the RT in pulmonary arteries. These phenomena were dependent on the contractile stimulus (phenylephrine or KCl). In conclusion, slow pulmonary vasoreactivity is a smooth muscle cell characteristic that can be enhanced by RhoA and NO or endothelium removal. These effects were counteracted by Rho kinase inhibition. We show a role for RhoA/Rho kinase and NO in the modulation of pulmonary vascular reactivity.