DECREASED SPINAL-CORD CONTENT OF CALCITONIN GENE-RELATED PEPTIDE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

Calcitonin gene-related peptide (CGRP), produced by alternative processing of the primary transcript of the calcitonin gene, is a potent vasodilator. We have shown that dietary calcium deficiency accompanied by decreased serum ionized calcium significantly decreases the neuronal content of CGRP in laminae I and II of the dorsal horn of the spinal cord in the growing rat. The spontaneously hypertensive rat (SHR) is characterized by decreased serum ionized calcium levels and is thought to most closely resemble human essential hypertension. To determine if the neuronal content of CGRP is decreased in the SHR compared to the Wistar-Kyoto (WKY) parent strain, CGRP was localized immunocytochemically in the dorsal horn of the spinal cord. The density of immunocytochemical staining was quantitated by computer-assisted image processing of laminae I and II of the upper thoracic spinal cord of 12-14 week old male SHR (n = 4) and WKY (n = 4) normotensive, control rats. The SHR had significantly decreased neuronal CGRP content compared to the WKY rats (107 +/- 5 vs 121 +/- 6 arbitrary units, P < 0.01). In contrast, the neuronal density of substance P (SP), which frequently co-exists with CGRP in this neuronal population, was not different between the two groups (SHR, 91 +/- 6 (n = 4) vs WKY, 88 +/- 3 arbitrary units (n = 4)). As expected, the SHR (n = 4) had a significantly higher tail-cuff systolic blood pressure than the WKY (n = 4) rats (214 +/- 10 vs 147 +/- 9 mmHg, P < 0.001) and serum ionized calcium was significantly lower in SHR (n = 8) vs WKY (n = 8) (5.25 +/- 0.04 vs 5.43 +/- 0.04 mg/dl, P < 0.01). In conclusion, SHR have a decrease in spinal cord laminae I and II content of CGRP which appears to be specific for CGRP since SP was not altered.