Enhanced Neuronal Expression of Calcitonin Gene–Related Peptide in Mineralocorticoid-Salt Hypertension

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Abstract
Dorsal root ganglia neuronal cell bodies synthesize the vasodilator neuropeptide calcitonin gene–related peptide and innervate the blood vessels and spinal cord sites (laminae I and II) involved in blood pressure regulation. We previously demonstrated that calcitonin gene–related peptide mRNA content is significantly decreased in dorsal root ganglia and that immunoreactive calcitonin gene–related peptide levels are reduced in laminae I and II of the dorsal horn of the spinal cord in the spontaneously hypertensive rat compared with Wistar-Kyoto control rats. To determine whether neuronal calcitonin gene–related peptide expression is also altered in mineralocorticoid-salt hypertension, we quantified calcitonin gene–related peptide mRNA levels in dorsal root ganglia and protein content in laminae I and II of the spinal cord in rats with mineralocorticoid-salt–induced hypertension. To control for pellet implantation, saline drinking water, and/or uninephrectomy, four normotensive groups were similarly studied. By Northern hybridization analysis, the ratio of calcitonin gene–related peptide mRNA to 18S rRNA was increased approximately fivefold in hypertensive rats (33±7) compared with each of the four normotensive control groups (average of the four groups, 6±0.5; P <.01, mineralocorticoid-salt group versus each group). The density of the peptide, quantified by computer-assisted image analysis, in laminae I and II in the hypertensive rats was also increased (66±1 versus average of the four groups, 46±2 arbitrary units; P <.001, mineralocorticoid-salt group versus each group). In conclusion, neuronal levels of calcitonin gene–related peptide mRNA and protein are increased in mineralocorticoid-salt hypertension. Therefore, increased neuronal synthesis and available stores of this potent vasodilator may be compensatory responses to and thus attenuate the blood pressure elevation in this experimental model of hypertension.