Catestatin in rat RVLM is sympathoexcitatory, increases barosensitivity, and attenuates chemosensitivity and the somatosympathetic reflex

Gaede AH, Pilowsky PM. Catestatin in rat RVLM is sympathoexcitatory, increases barosensitivity, and attenuates chemosensitivity and the somatosympathetic reflex. Am J Physiol Regul Integr Comp Physiol 299: R1538-R1545, 2010. First published October 6, 2010; doi:10.1152/ajpregu.00335.2010.-The fundamental role and corollary effects of neuropeptides that govern cardiorespiratory control in the brain stem are poorly understood. One such regulatory peptide, catestatin [Cts, human chromogranin A-(352-372)], noncompetitively inhibits nicotinic-cholinergic-stimulated catecholamine release. Previously, we demonstrated the presence of chromogranin A mRNA in brain stem neurons that are important for the maintenance of arterial pressure. In the present study, using immunofluorescence histochemistry, we show that Cts immunoreactivity is colocalized with tyrosine hydroxylase in C1 neurons of the rostral ventrolateral medulla (RVLM, n = 3). Furthermore, we investigated the effects of Cts on resting blood pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and adaptive reflexes. Cts (1 mM in 50 nl or 100 mu M in 50-100 nl) was microinjected into the RVLM in urethane-anesthetized, vagotomized, ventilated Sprague-Dawley rats (n = 19). Cardiovascular responses to stimulation of carotid baroreceptors, peripheral chemoreceptors, and the sciatic nerve (somatosympathetic reflex) were analyzed. Cts (1 mM in 50 nl) increased resting arterial pressure (28 +/- 3 mmHg at 2 min postinjection), sympathetic nerve activity (15 +/- 3% at 2 min postinjection), and phrenic discharge amplitude (31 +/- 4% at 10 min postinjection). Cts increased sympathetic barosensitivity 40% (slope increased from -0.05 +/- 0.01 before Cts to -0.07 +/- 0.01 after Cts) and attenuated the somatosympathetic reflex [1st peak: 36% (from 132 +/- 32.1 to 84.0 +/- 17.0 mu V); 2nd peak: 44% (from 65.1 +/- 21.4 to 36.6 +/- 14.1 mu V)] and chemoreflex (blood pressure response to anoxia decreased 55%, sympathetic response decreased 46%). The results suggest that Cts activates sympathoexcitatory bulbospinal neurons in the RVLM and plays an important regulatory role in adaptive reflexes.