Katki K A, Supowit S C, DiPette D J
Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
Hypertension. 2001 Sep;38(3 Pt 2):679-82. doi: 10.1161/hy09t1.095761.
Calcitonin gene-related peptide (CGRP) and substance P are known to play a counterregulatory role in acquired models of salt-dependent hypertension. In contrast, neuronal production of these peptides is decreased in the spontaneously hypertensive rat, which may contribute to the elevated blood pressure. To determine the role played by CGRP and substance P in Dahl-salt hypertension, 4- to 6-week-old male salt-resistant (DR) and salt-sensitive (DS) rats were divided into 4 groups (n=5/group) and pair-fed low-salt (0.2% NaCl) (DR/LS and DS/LS) and high-salt (8% NaCl) diets (DR/HS and DS/HS) for 3 weeks. After 3 weeks, all the rats had venous (for drug administration) and arterial (for blood pressure monitoring) catheters surgically implanted and were studied in the conscious and unrestrained state. Mean arterial pressure was significantly higher in the DS/HS rats animals (185.8+/-1.6 mm Hg, P<0.001). Intravenous administration of CGRP and SP receptor antagonists was without effect in any of the groups studied. CGRP and SP mRNA content from dorsal root ganglia were not significantly different between the groups. Whereas immunoreactive CGRP was decreased in the DS groups (DS/HS, 9.4+/-0.4 pg/microgram protein; DS/LS, 11.1+/-0.8 pg/microgram protein; P<0.01) compared with the DR groups (DR/HS, 13.9+/-0.6 pg/microgram protein; DR/LS, 14.6+/-0.6 pg/microgram protein), neuronal SP production was similar between all the groups. Thus, CGRP and substance P do not play a counterregulatory role in Dahl-salt hypertension. The decrease in neuronal CGRP expression in DS rats appears to be genetically determined as in SHR, however, and may contribute to the increase in blood pressure following salt-loading.
已知降钙素基因相关肽（CGRP）和P物质在盐依赖性高血压的获得性模型中发挥反调节作用。相比之下，在自发性高血压大鼠中，这些肽的神经元生成减少，这可能导致血压升高。为了确定CGRP和P物质在Dahl盐敏感性高血压中所起的作用，将4至6周龄的雄性盐抵抗（DR）和盐敏感（DS）大鼠分为4组（每组n = 5），并配对喂养低盐（0.2% NaCl）（DR/LS和DS/LS）和高盐（8% NaCl）饮食（DR/HS和DS/HS）3周。3周后，所有大鼠均通过手术植入静脉导管（用于给药）和动脉导管（用于监测血压），并在清醒和不受约束的状态下进行研究。DS/HS组大鼠的平均动脉压显著更高（185.8±1.6 mmHg，P<0.001）。静脉注射CGRP和SP受体拮抗剂对任何研究组均无影响。背根神经节中CGRP和SP的mRNA含量在各组之间无显著差异。与DR组（DR/HS，13.9±0.6 pg/微克蛋白质；DR/LS，14.6±0.6 pg/微克蛋白质）相比，DS组（DS/HS，9.4±0.4 pg/微克蛋白质；DS/LS，11.1±0.8 pg/微克蛋白质）中免疫反应性CGRP降低（P<0.01），而所有组之间神经元SP的生成相似。因此，CGRP和P物质在Dahl盐敏感性高血压中不发挥反调节作用。然而，与自发性高血压大鼠一样，DS大鼠中神经元CGRP表达的降低似乎是由基因决定的，并且可能导致盐负荷后血压升高。
