Burton H W, Walker J A
Department of Physical Therapy and Exercise Science, State University of New York at Buffalo 14214.
Microvasc Res. 1994 Jul;48(1):85-95. doi: 10.1006/mvre.1994.1040.
This study investigated the responses of regenerating arterioles in grafted skeletal muscle to the endothelium-dependent dilator acetylcholine (ACh); the substrate for endothelium-derived relaxing factor (EDRF), L-arginine (L-Arg); and sodium nitroprusside (SNP). Additionally, responses of graft arterioles to the endothelium-independent substances adenosine (Ado) and norepinephrine (NE) were measured. The retractor muscle of hamsters was removed, placed in a myotoxic solution, and grafted into its original site. The graft revascularized spontaneously by sprouting of vessels in surrounding tissue. Quantification of changes in arteriolar luminal diameter was accomplished using in vivo video microscopy at 30, 45, and 60 days postgrafting. In 30-day grafts, there was little or no response to topically applied ACh or L-Arg. By 45 days, arteriole response to 10(-6), 10(-5), and 10(-4) M ACh and 10(-4) L-Arg was 0, 4, 20, and 17% of the control response, respectively. SNP (10(-6)-10(-4) M) produced approximately 50% of the control response at both 30 and 45 days. By 60 days the response of graft arterioles to ACh, L-Arg, and SNP was not different from controls. Arteriolar response in 30-day grafts to Ado (10(-6)-10(-4) M) was significantly attenuated, but was not different from control by 45 days. Responsiveness of arterioles to NE had recovered to control levels by 30 days postgrafting. These data indicate that the restoration of endothelium-dependent regulation of arteriolar dilation lags behind endothelium-independent, receptor-mediated mechanisms. The diminished response of regenerating arterioles may be related to dysfunctions in both the synthetic pathway for EDRF and the guanylate cyclase/cGMP mechanism for vascular smooth muscle cell relaxation and/or flow-dependent mechanisms of blood flow regulation.
本研究调查了移植骨骼肌中再生小动脉对内皮依赖性舒张剂乙酰胆碱（ACh）、内皮源性舒张因子（EDRF）的底物L-精氨酸（L-Arg）以及硝普钠（SNP）的反应。此外，还测量了移植小动脉对非内皮依赖性物质腺苷（Ado）和去甲肾上腺素（NE）的反应。将仓鼠的牵张肌切除，置于肌毒性溶液中，然后移植回其原始部位。移植组织通过周围组织血管的芽生自发地重新血管化。在移植后30天、45天和60天，使用体内视频显微镜对小动脉管腔直径的变化进行量化。在移植30天的组织中，对局部应用的ACh或L-Arg几乎没有反应。到45天时，小动脉对10^(-6)、10^(-5)和10^(-4)M ACh以及10^(-4)L-Arg的反应分别为对照反应的0%、4%、20%和17%。SNP（10^(-6)-10^(-4)M）在30天和45天时均产生约50%的对照反应。到60天时，移植小动脉对ACh、L-Arg和SNP的反应与对照无差异。移植30天的组织中小动脉对Ado（10^(-6)-10^(-4)M）的反应明显减弱，但到45天时与对照无差异。移植后30天，小动脉对NE的反应性已恢复到对照水平。这些数据表明，小动脉舒张的内皮依赖性调节的恢复落后于非内皮依赖性、受体介导的机制。再生小动脉反应减弱可能与EDRF合成途径以及血管平滑肌细胞舒张的鸟苷酸环化酶/cGMP机制和/或血流调节的流量依赖性机制的功能障碍有关。
