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Catestatin, a chromogranin A-derived peptide, is sympathoinhibitory and attenuates sympathetic barosensitivity and the chemoreflex in rat CVLM.

Abstract
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.
AuthorsAndrea H Gaede, Paul M Pilowsky
JournalAmerican journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 302 Issue 3 Pg. R365-72 (Feb 01 2012) ISSN: 1522-1490 [Electronic] United States
PMID22129620 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chromogranin A
  • Peptide Fragments
  • Sympatholytics
  • chromogranin A (344-364)
Topics
  • Animals
  • Baroreflex (drug effects, physiology)
  • Blood Pressure (drug effects, physiology)
  • Chemoreceptor Cells (cytology, drug effects, physiology)
  • Chromogranin A (administration & dosage, metabolism, pharmacology)
  • Heart Rate (drug effects, physiology)
  • Hypoxia (physiopathology)
  • Male
  • Medulla Oblongata (cytology, drug effects, physiology)
  • Microinjections
  • Models, Animal
  • Peptide Fragments (administration & dosage, metabolism, pharmacology)
  • Phrenic Nerve (drug effects, physiology)
  • Rats
  • Rats, Sprague-Dawley
  • Sympathetic Nervous System (drug effects, physiology)
  • Sympatholytics (administration & dosage, pharmacology)

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