ENHANCED NEURONAL EXPRESSION OF CALCITONIN-GENE-RELATED PEPTIDE IN MINERALOCORTICOID-SALT HYPERTENSION

Dorsal root ganglia neuronal cell bodies synthesize the vasodilator ne uropeptide calcitonin gene-related peptide and innervate the blood ves sels and spinal cord sites (laminae I and II) involved in blood pressu re regulation. We previously demonstrated that calcitonin gene-related peptide mRNA content is significantly decreased in dorsal root gangli a and that immunoreactive calcitonin gene-related peptide levels are r educed in laminae I and II of the dorsal horn of the spinal cord in th e spontaneously hypertensive rat compared with Wistar-Kyoto control ra ts. To determine whether neuronal calcitonin gene-related peptide expr ession is also altered in mineralocorticoid-salt hypertension, we quan tified calcitonin gene-related peptide mRNA levels in dorsal root gang lia and protein content in laminae I and II of the spinal cord in rats with mineralocorticoid-salt-induced hypertension. To control for pell et implantation, saline drinking water, and/or uninephrectomy, four no rmotensive groups were similarly studied. By Northern hybridization an alysis, the ratio of calcitonin gene-related peptide mRNA to 18S rRNA was increased approximately fivefold in hypertensive rats (33+/-7) com pared with each of the four normotensive control groups (average of th e four groups, 6+/-0.5; P<.01, mineralocorticoid-salt group versus eac h 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 or group versus each group). In conclusion, neuronal levels of calcitonin gene-related peptide mRNA an d protein are increased in mineralocorticoid-salt hypertension. Theref ore, increased neuronal synthesis and available stores of this potent vasodilator may be compensatory responses to and thus attenuate the bl ood pressure elevation in this experimental model of hypertension.