Role of calcitonin gene-related peptide and substance P in Dahl-salt hypertension

Calcitonin gene-related peptide (CGRP) and substance P are known to play a counterregulatory role in acquired models of salt-dependent hypertension. I n contrast, neuronal production of these peptides is decreased in the spont aneously hypertensive rat, which may contribute to the elevated blood press ure. To determine the role played by CGRP and substance P in Dahl-salt hype rtension, 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 pr essure 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 antagonis ts was without effect in any of the groups studied. CGRP and SP mRNA conten t from dorsal root ganglia were not significantly different between the gro ups. Whereas immunoreactive CGRP was decreased in the DS groups (DS/HS, 9.4 +/-0.4 pg/mug protein; DS/LS, 11.1 +/-0.8 pg/mug protein; P <0.01) compare d with the DR groups (DR/HS, 13.9 +/-0.6 pg/mug protein; DR/LS, 14.6 +/-0.6 pg/mug protein), neuronal SP production was similar between all the groups . Thus, CGRP and substance P do not play a counterregulatory role in Dahl-s alt hypertension. The decrease in neuronal CGRP expression in DS rats appea rs to be genetically determined as in SHR, however, and may contribute to t he increase in blood pressure following salt-loading.