Hypertension is a major cause of morbidity. The
neuropeptide catestatin [human
chromogranin A-(352-372)] is a
peptide product of the vesicular
protein chromogranin A. Studies in the periphery and in vitro studies show that
catestatin blocks
nicotine-stimulated
catecholamine release and interacts with β-
adrenoceptors and
histamine receptors.
Catestatin immunoreactivity is present in the rostral ventrolateral medulla (RVLM), a key site for blood pressure control in the brain stem. Recently, we reported that microinjection of
catestatin into the RVLM is sympathoexcitatory and increases barosensitivity. Here, we report the effects of microinjection of
catestatin (1 mM, 50 nl) into the caudal ventrolateral medulla (CVLM) in
urethane-anesthetized, bilaterally vagotomized, artificially ventilated Sprague-Dawley rats (n = 8). We recorded resting arterial pressure, splanchnic sympathetic nerve activity, phrenic nerve activity, heart rate, and measured cardiovascular homeostatic reflexes. Homeostatic reflexes were evaluated by measuring cardiovascular responses to carotid baroreceptor and peripheral chemoreceptor activation.
Catestatin decreased basal levels of arterial pressure (-23 ± 4 mmHg), sympathetic nerve activity (-26.6 ± 5.7%), heart rate (-19 ± 5 bpm), and phrenic nerve amplitude (-16.8 ± 3.3%).
Catestatin caused a 15% decrease in phrenic inspiratory period (T(i)) and a 16% increase in phrenic expiratory period (T(e)) but had no net effect on the phrenic interburst interval (T(tot)).
Catestatin decreased sympathetic barosensitivity by 63.6% and attenuated the peripheral chemoreflex (sympathetic nerve response to brief
hypoxia; range decreased 39.9%; slope decreased 30.1%). The results suggest that
catestatin plays an important role in central cardiorespiratory control.