Reduced endothelial vasomotor function and enhanced neointimal formation after vascular injury in a rat model of blood pressure lability.
Increased short-term blood pressure variability is known to be associated with hypertensive target organ damage. Sinoaortic denervation (SAD) induces a marked increase in blood pressure lability without affecting the average blood pressure level. The aim of this study was to investigate the effects of blood pressure lability on endothelial vasomotor function and neointimal formation after balloon injury in SAD rats. Direct longterm measurement of mean arterial pressure showed no significant difference in the average of mean arterial pressure between the SAD group and sham-operated control group. In contrast, the standard deviation of mean arterial pressure, as an index of blood pressure lability, was 3-fold greater in SAD rats. To study endothelial function, isometric tension of aortic rings was measured 4 weeks after SAD or sham operation. Endothelium-dependent vasorelaxation induced by acetylcholine was significantly reduced in the SAD group (20% reduction at maximum relaxation). Endothelium-independent vasorelaxation induced by sodium nitroprusside was similar in each group. Acetylcholine-induced NO release from aortic rings was significantly reduced in the SAD group. Next, we examined neointimal formation in carotid arteries in SAD and sham-operated rats at 2 weeks after balloon injury. The neointimal-to-medial area ratio in the SAD group was 50% higher than that in the sham-operated group. The percentage of proliferating cell nuclear antigen-positive cells in the intima was significantly higher in the SAD group. These findings suggest that increased blood pressure lability, independently of average blood pressure level, impairs endothelial function by inhibiting NO production, enhances neointimal formation after balloon injury, and may thereby contribute to atherogenesis.
Eto
Masato
M
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Toba
Kenji
K
Akishita
Masahiro
M
Kozaki
Koichi
K
Watanabe
Tokumitsu
T
Kim
Seungbum
S
Hashimoto
Masayoshi
M
Sudoh
Noriko
N
Yoshizumi
Masao
M
Ouchi
Yasuyoshi
Y
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure; D020212:Carotid Artery Injuries / Q000473:pathology* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D006339:Heart Rate; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017539:Tunica Intima / Q000473:pathology; D014664:Vasodilation / Q000502:physiology