Attenuation of receptor-dependent and -independent vasoconstriction in the human radial artery☆

Abstract

The irreversible calmodulin antagonist fluphenazine has potential to be developed as an inhibitor of contraction in arterial graft vessels. The involvement of Rho kinase indicates that other vasoconstrictors and surgical stress can sensitize radial artery to vasopressin-induced contraction. Strategies targeting this pathway also have future potential.

Intraradial administration of fasudil inhibits augmented Rho kinase activity to effectively dilate the spastic radial artery during coronary artery bypass grafting surgery

“…The following reagents were used in the present study: 5-hydroxytryptamine (5-HT; serotonin), noradrenalin (NA), papaverine, and mouse monoclonal anti-MLC antibody (M4401; Sigma, St Louis, Mo); dithiothreitol, trichloroacetic acid, and acetone (Wako Pure Chemicals, Osaka, Japan); rabbit polyclonal anti-phospho (Thr 853 )-MYPT1 (36-003) antibody (Upstate Biotechnology, Lake Placid, NY); rabbit polyclonal anti-MYPT1 antibody (PRB-457C; Covance, Berkley, Calif); rabbit polyclonal antiphospho (Ser 19 )-MLC (3675) antibody (Cell Signaling, Danvers, Mass); fasudil (HA-1077; Asahi Chemical Industry, Fuji, Japan); verapamil and olprinone (Eizai Pharm, Inc, Tokyo, Japan); and glyceryl trinitrate (nitroglycerin; Astellas Pharma, Inc, Tokyo, Japan).…”

“…22 Fixed tissues were homogenized in a homogenization buffer of the following composition: 20 mmol/L Tris/HCl (pH 7.5); 100 mmol/L NaF; 1 mmol/L Na 3 VO 4 ; 1 mmol/L phenylmethylsulfonyl fluoride; 0.1% sodium dodecylsulfate; 2 mmol/L ethyleneglycol-bis-(b-aminoethylether)-N,N,N 0 ,N 0 -tetraacetic acid; 0.5% NP-40; and 20 mg/ml each of leupeptin and aprotinin. The samples (80 mg of protein) were separated on 8% (for MYPT1) or 15% (for MLC) sodium dodecylsulfate-polyacrylamide gel electrophoresis, followed by Western blot analysis with either phospho(Thr 853 )-MYPT1-or phospho(Ser 19 )-MLC-specific antibodies. The same samples were also analyzed by means of Western blotting with antibodies that recognize both phospho-and non-phospho-proteins.…”

“…ROCK-dependent MLCP inhibition is implicated in pathological vascular hypercontractile conditions; clinical trials have demonstrated that fasudil, a ROCK inhibitor, is effective in suppressing vasospasm after subarachnoid hemorrhage and coronary artery spasm. [14][15][16][17][18] Recently, it has been reported that ROCK inhibitors, such as fasudil and Y27632, prevent agonist-induced vasoconstriction in isolated human RAs in vitro 19,20 and that the mRNA and protein expression of Rho and ROCK in the RA was increased compared with that seen in the internal thoracic artery. 21 In the present study we first examined the efficacy of fasudil on vasoactive agonistinduced contraction and MLCP inhibition in isolated RA rings.…”

Rho-kinase, the forgotten link?

“…Therefore, catheter-based techniques have to be compared with the 'old fashioned' conventional way of surgery. This does not mean that new approaches should not be pushed further.Again, we congratulate Lentini and co-workers for their good results and valuable discussion [1]. …”

“…I congratulate Shackcloth and co-workers for their article on receptor-dependent and independent vasoconstriction in the human radial artery [1]. I find of interest their work on the role of Rho-kinase on radial artery graft spasm following coronary artery bypass grafting.…”