Busija D W, Chen J
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083.
J Dev Physiol. 1992 Aug;18(2):67-72.
We investigated effects of calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A (NKA) on pial arterioles in newborn pigs. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. Initial diameters were approximately 100 microns. Calcitonin-gene related peptide dilated pial arterioles by 22 +/- 8% at 10(-9)M and by 34 +/- 6% at 10(-8)M (n = 8), and this response was not significantly altered by prior administration of indomethacin (5mg/kg, iv) (n = 6) or administration of NG-methyl-L-arginine (5mg/kg, iv, and 10(-3)M in CSF) (n = 10). Substance P dilated arterioles at 10(-10)M through 10(-5)M (maximal response = 23 +/- 3%) (n = 6), and this response was unaffected by indomethacin administration (n = 6). In contrast, NG-methyl-L-arginine blocked much of the pial arteriolar dilation to SP. Unlike the other two peptides, NKA did not change pial arteriolar diameter. Radioimmunoassay determinations indicated that cerebrospinal fluid levels of 6-keto-prostaglandin F1 and prostaglandin E2 did not change appreciably during application of CGRP or SP. We conclude that CGRP and SP but not NKA are dilator stimuli in the piglet pial circulation. Dilation by CGRP probably involves direct activation of receptors on vascular smooth muscle, while SP probably partially dilates pial arterioles via release of an endothelium-dependent relaxing factor.
我们研究了降钙素基因相关肽（CGRP）、P物质（SP）和神经激肽A（NKA）对新生猪软脑膜小动脉的影响。使用封闭的颅窗和活体显微镜测定软脑膜小动脉直径。初始直径约为100微米。降钙素基因相关肽在10^(-9)M时使软脑膜小动脉扩张22±8%，在10^(-8)M时扩张34±6%（n = 8），预先给予吲哚美辛（5mg/kg，静脉注射）（n = 6）或给予NG-甲基-L-精氨酸（5mg/kg，静脉注射，脑脊液中为10^(-3)M）（n = 10）后，这种反应无明显改变。P物质在10^(-10)M至10^(-5)M时使小动脉扩张（最大反应 = 23±3%）（n = 6），给予吲哚美辛后这种反应不受影响（n = 6）。相比之下，NG-甲基-L-精氨酸阻断了大部分软脑膜小动脉对P物质的扩张。与其他两种肽不同，NKA未改变软脑膜小动脉直径。放射免疫测定表明，在应用CGRP或P物质期间，脑脊液中6-酮-前列腺素F1和前列腺素E2的水平没有明显变化。我们得出结论，CGRP和P物质而非NKA是仔猪软脑膜循环中的扩张刺激物。CGRP引起的扩张可能涉及血管平滑肌上受体的直接激活，而P物质可能通过释放内皮依赖性舒张因子使软脑膜小动脉部分扩张。
