4.6 Article

Direct Vasoactive Effects of the Chromogranin A (CHGA) Peptide Catestatin in Humans In Vivo

Journal

CLINICAL AND EXPERIMENTAL HYPERTENSION
Volume 32, Issue 5, Pages 278-287

Publisher

TAYLOR & FRANCIS INC
DOI: 10.3109/10641960903265246

Keywords

catestatin; chromogranin A; vasodilation; veins

Funding

  1. NIH [NIH RR00827]
  2. Comprehensive Research Center of Excellence in Minority Health and Health Disparities (CRCOE, NIH) [MD00020]
  3. National Institutes of Health
  4. Department of Veterans Affairs
  5. NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000827] Funding Source: NIH RePORTER
  6. NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES [P60MD000220] Funding Source: NIH RePORTER
  7. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL058120] Funding Source: NIH RePORTER

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Catestatin is a bioactive peptide of chromogranin A (CHGA) that is co-released with catecholamines from secretory vesicles. Catestatin may function as a vasodilator and is diminished in hypertension. To evaluate this potential vasodilator in vivo without systemic counterregulation, we infused catestatin to target concentrations of similar to 50, similar to 500, similar to 5000 nM into dorsal hand veins of 18 normotensive men and women, after pharmacologic venoconstriction with phenylephrine. Pancreastatin, another CHGA peptide, was infused as a negative control. After preconstriction to similar to 69%, increasing concentrations of catestatin resulted in dose-dependent vasodilation (P = 0.019), in female subjects (to similar to 44%) predominantly. The EC50 (similar to 30 nM) for vasodilation induced by catestatin was the same order of magnitude to circulating endogenous catestatin (4.4 nM). No vasodilation occurred during the control infusion with pancreastatin. Plasma CHGA, catestatin, and CHGA-to-catestatin processing were then determined in 622 healthy subjects without hypertension. Female subjects had higher plasma catestatin levels than males (P = 0.001), yet lower CHGA precursor concentrations (P = 0.006), reflecting increased processing of CHGA-to-catestatin (P < 0.001). Our results demonstrate that catestatin dilates human blood vessels in vivo, especially in females. Catestatin may contribute to sex differences in endogenous vascular tone, thereby influencing the complex predisposition to hypertension.

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