Sevoflurane inhibits angiotensin II-induced Rho kinase-mediated contraction of vascular smooth muscle from spontaneously hypertensive rat.

Abstract

PURPOSE:

Angiotensin II (Ang II)-induced vasoconstriction is mediated by changes in intracellular free Ca(2+) concentration ([Ca(2+)](i)) and myofilament Ca(2+) sensitivity. Protein kinase C- and Rho kinase-mediated signaling pathways are proposed for the regulation of the Ca(2+) sensitization mechanisms. We have demonstrated that sevoflurane inhibits Rho kinase-mediated contraction of isolated rat aortic smooth muscle. A recent study demonstrated that Rho-kinase mediated Ca(2+) sensitization was involved in the pathophysiology of hypertension. This study was designed to investigate the effects of sevoflurane on Ang II-induced Rho kinase-mediated vascular contraction in spontaneously hypertensive rats (SHR).

METHODS:

The effects of sevoflurane on vasoconstriction, increase in [Ca(2+)](i), and membrane translocation of Rho kinase in response to Ang II were investigated in normotensive Wistar-Kyoto rats (WKY) and SHR, using an isometric force transducer, a fluorometer, and Western blotting, respectively.

RESULTS:

The inhibitory effects of sevoflurane on Ang II (10(-7)M)-induced contraction were greater (P < 0.05) in SHR than in WKY at the highest concentration of sevoflurane (5.1%). Y27632 (3 × 10(-7)M), a specific inhibitor of Rho kinase, inhibited the Ang II-induced contraction in SHR, but not in WKY. Sevoflurane did not affect the increases in [Ca(2+)](i) in response to Ang II in either strain. Ang II stimulated Rho kinase activity in SHR, which was almost abolished by sevoflurane at a concentration of 5.1% (P < 0.05).

CONCLUSIONS:

These findings suggest that the inhibition of the Ang II-induced contraction by sevoflurane in SHR may be, at least in part, due to the attenuation of the Rho kinase-mediated signaling pathway.

• Authors: Nobuhiko Uematsu, Koji Ogawa, Yasuyuki Tokinaga, Kazuaki Tange, Yoshio Hatano
• Journal: Journal of anesthesia (J Anesth) Vol. 25 Issue 3 Pg. 398-404 (Jun 2011) ISSN: 1438-8359 [Electronic] Japan
• PMID: 21409351 (Publication Type: Journal Article)

Chemical References

• Amides
• Anesthetics, Inhalation
• Enzyme Inhibitors
• Methyl Ethers
• Pyridines
• Angiotensin II
• Y 27632
• Sevoflurane
• rho-Associated Kinases
• Calcium

Topics

• Amides (pharmacology)
• Anesthetics, Inhalation (pharmacology)
• Angiotensin II (antagonists & inhibitors, pharmacology)
• Animals
• Aorta, Thoracic (drug effects)
• Blood Pressure (drug effects)
• Calcium (metabolism)
• Calcium Signaling (drug effects)
• Enzyme Inhibitors (pharmacology)
• In Vitro Techniques
• Isometric Contraction (drug effects)
• Male
• Methyl Ethers (pharmacology)
• Muscle Contraction (drug effects)
• Muscle, Smooth, Vascular (drug effects)
• Protein Transport
• Pyridines (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Sevoflurane
• rho-Associated Kinases (antagonists & inhibitors)