TY - JOUR
T1 - Endogenous vascular remodeling in ischemic skeletal muscle
T2 - A role for nitric oxide
AU - Buckwalter, John B.
AU - Curtis, Valerie C.
AU - Valic, Zoran
AU - Ruble, Stephen B.
AU - Clifford, Philip S.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-L-arginine methyl ester (a NO synthase inhibitor) or a control solution (N-nitro-D-arginine methyl ester or phenylephtine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly (P < 0.05) lower in the L-NAME-treated group than in controls for the duration of the study: 48 ± 4 vs. 60 ± 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially (P < 0.05) shorter in the L-NAME-treated group: 539 ± 67 vs. 889 ± 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.
AB - To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-L-arginine methyl ester (a NO synthase inhibitor) or a control solution (N-nitro-D-arginine methyl ester or phenylephtine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly (P < 0.05) lower in the L-NAME-treated group than in controls for the duration of the study: 48 ± 4 vs. 60 ± 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially (P < 0.05) shorter in the L-NAME-treated group: 539 ± 67 vs. 889 ± 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.
KW - Angiogenesis
KW - Arteriogenesis
KW - Blood flow
KW - Exercise
KW - Rabbits
UR - http://www.scopus.com/inward/record.url?scp=0037372559&partnerID=8YFLogxK
U2 - 10.1152/japplphysiol.00378.2002
DO - 10.1152/japplphysiol.00378.2002
M3 - Article
C2 - 12391140
AN - SCOPUS:0037372559
SN - 8750-7587
VL - 94
SP - 935
EP - 940
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 3
ER -