Mechanisms of peripheral vasodilatory dysfunction during exercise in chronic heart failure

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10670672
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: FUKUSHIMA MEDICAL UNIVERSITY
• Principal Investigator: MAEHARA Kazuhira Fukushima Medical University, First Dept. of Internal Med., Associate Prof., 医学部, 助教授 (90181817)
• Co-Investigator(Kenkyū-buntansha): MARUYAMA Yukio Fukushima Medical University, First Dept. of Internal Med., Prof., 医学部, 教授 (90004712)
• Project Period (FY): 1998 – 1999
• Keywords: vasodilatory dysfunction / chronic heart failure / exercise hyperemia / metabolic vasodilation / nitric oxide / K-ATP channel

Research Abstract

Increased peripheral vascular tone and decreased vasodilatory capacity would be major determinants of decreased exercise capacity in chronic heart failure. However, the precise mechanisms of these abnormalities have not been elucidated. We investigated changes of exercise hyperemia by various blockers in normal rats and rats with chronic heart failure induce by myocardial infraction. Normal rats swan for 3 min 4 days after Doppler flow probe on abdominal aorta and aortic cannula were chronically instrumented. NO synthase inhibitor, L-NAME and K-ATP channel blocker, glibenclamide reduced exercise hyperemia, but adenosine deaminase and cyclooxygenase inhibitor, indomethacin did not. The rate of decrease in hindquarter vascular resistance was rather larger in L-NAME exercise than control exercise, and exercise hyperemia response was completely restored by constant infusion of nitroprusside. It indicated that basal NO release is necessary to maintain exercise blood flow but NO production d uring exercise, if any, does not maintain exercise, and exercise hyperemia response was completely restored by constant infusion of nitroprusside. It indicated that basal NO release is necessary to maintain exercise blood flow but NO production during exercise, if any, does not play a significant role on exercise hyperemia response. K-ATP channel would partially contribute exercise hyperemia, but adenosine and prostaglandins would not be main mediators of metabolic vasodilation during exercise. In chronic heart failure model, it was very difficult to survive after chronic instrumentation. Therefore, we evaluated changes of peripheral vascular resistance during electrically stimulated muscle contraction after anesthesia. Transrectal electrical stimulation of cauda equina induced approximately 3 fold increase in hindquarter blood flow, which blood flow response would be equivalent to submaximal exercise level. As a result, metabolic vasodilation seems not to be impaired despite endothelium-dependent vasodilation induced by acetylcholine is significantly reduced in rats with chronic heart failure 4 weeks after myocardial infraction.