RhoA/Rho kinase and nitric oxide modulate the agonist-induced pulmonary artery diameter response time.
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.
Boer
Christa
C
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit Medical Center, 1081 BT Amsterdam, The Netherlands. c.boer.physiol@med.vu.nl
van der Linden
Peter J W
PJ
Scheffer
Gert Jan
GJ
Westerhof
Nico
N
de Lange
Jaap J
JJ
Sipkema
Pieter
P
D000109:Acetylcholine / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology / Q000379:methods; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008839:Microelectrodes; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000502:physiology; D012680:Sensitivity and Specificity; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases
D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D011725:Pyridines; C108830:Y 27632; D019335:Nitroarginine; D009569:Nitric Oxide; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000109:Acetylcholine