Vasodilatory effect of subsequent administration of fasudil, a rho-kinase inhibitor, surpasses that of nitroglycerin at the concentric coronary stenosis in patients with stable angina pectoris.
BACKGROUND
Recent studies have suggested that the Rho/Rho-kinase mediated pathway (Rho-kinase pathway) regulates the vasomotion of arteries in pathological conditions. However, it remains unclear regarding whether this pathway regulates the coronary vasomotion of atherosclerotic lesions.


RESULTS
The coronary diameter at the concentric stenotic site, which is considered to reflect the whole circumferential atherosclerosis, in patients with stable angina pectoris (SAP; n=11) and the control site in patients with SAP and chest pain syndrome (CPS; n=9), was measured at baseline and after the intracoronary administration of nitroglycerin (200 microg) and the subsequent intravenous infusion of fasudil (30 mg for 30 min), a Rho-kinase inhibitor, during coronary angiography. The change in the diameter with fasudil at the concentric stenotic site (22.0+/-10.0%) was significantly higher than that with nitroglycerin (4.7+/-6.0%, p<0.001) in patients with SAP. Meanwhile, the vasodilatory effect of nitroglycerin and fasudil at the control site was similar in both group of patients (25.5+/-17.3% and 21.9+/-14.9% in SAP and 34.4+/-20.8% and 33.2+/-23.6% in CPS, respectively).


CONCLUSIONS
The vasodilatory effect of the subsequent administration of fasudil surpassed that of nitroglycerin at the concentric coronary stenosis in patients with SAP, thus suggesting that the Rho-kinase pathway regulates the coronary vasomotion of atherosclerotic lesions.
Department of Internal Medicine and Cardiology, Tama-Nagayama Hospital, Nippon Medical School, Tokyo, Japan. otsuka@nms.ac.jp
Toshiaki
T
Otsuka
Chikao
C
Ibuki
Takeshi
T
Suzuki
Kensuke
K
Ishii
Eitaro
E
Kodani
Hirotsugu
H
Atarashi
Hiroshi
H
Kishida
Teruo
T
Takano
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D000792:Angiography / Q000379:methods; D002637:Chest Pain / Q000188:drug therapy / Q000503:physiopathology; D023921:Coronary Stenosis / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D054460:rho-Associated Kinases
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D014665:Vasodilator Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D005996:Nitroglycerin; C049347:fasudil