Neuroscience Letters, 131 (1991) 183-186 © 1991 Elsevier Scientific Publishers Ireland Ltd. 0304-3940/91/$ 03.50 ADONIS 0304394091005741 NSL 08089 183 Decreased spinal cord content of calcitonin gene-related peptide in the spontaneously hypertensive rat Karin N. Westlund 1, Donald J. DiPette 2, Jay Carson 2 and O.Bryan Holland 2 Departments of 1Anatomy and Neurosciences, Marine Biomedical Institute and 2 Medicine, Division of Endocrinology, Metabolism and Hypertension, University of Texas Medical Branch, Galveston, TX 77550 (U.S.A.) (Received 5 March 1991; Revised version received 27 June 1991; Accepted I July 1991) Key words: Calcitonin gene-related peptide; Calcium; Sensory afferent; Spinal cord; Hypertension Calcitonin gene-related peptide (CGRP), produced by alternative processing of the primary transcript of the calcitonin gene, is a potent vasodila- tor. 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 wo not altered. Calcitonin gene-related peptide (CGRP), a 37 amino acid neuropeptide, is a potent vasodilator produced by alternative processing of the primary transcript of the calcitonin gene, so changes in calcium homeostasis that alter calcitonin synthesis might be expected to change CGRP production in a similar fashion. Alterations in calcium homeostasis such as decreased serum ionized calcium and increased serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 levels, have been reported in both human and experimental hypertension, but appear to be particularly prominent in low-renin hypertension [3, 11, 17]. Some patients with hypertension and animal models of experimental hypertension, espe- cially those with low-renin hypertension, exhibit a reduc- tion in blood pressure following dietary calcium supple- mentation [5, 11, 17]. CGRP has been identified in multiple species includ- ing rat and man. Among its multiple biological proper- Correspondence: K.N. Westlund, 200 University, University of Texas Medical Branch, Galveston, TX 77550, U.S.A. ties, CGRP has been shown to possess marked cardio- vascular activity. In the conscious rat the systemic ad- ministration of CGRP results in a dose-dependent de- crease in blood pressure, which is mediated by peripheral vasodilation [7]. In addition, CGRP has been shown to have potent chronotropic and inotropic effects [1, 10]. Immunocytochemical and radioimmunoassay techni- ques have identified CGRP-containing nerve fibers throughout the cardiovascular system [10]. Thus, CGRP may play an important role in blood pressure and re- gional blood flow regulation. In a previous study from our laboratories [8], quanti- tative immunocytochemical techniques were utilized to evaluate changes in CGRP content in laminae I and II of the dorsal horn of the spinal cord of rats during changes in calcium balance induced by changing dietary calcium intake. Lowered dietary calcium intake de- creased dorsal horn CGRP content in young, growing rats, while high calcium diet significantly increased CGRP content, in both young and adult rats. These changes were more dramatic in young, growing rats than in adult rats, perhaps reflecting the greater calcium deft-