title: Direct vasoactive effects of the chromogranin A (CHGA) peptide catestatin in humans in vivo.
abstract: 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 approximately 50, approximately 500, approximately 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 approximately 69%, increasing concentrations of catestatin resulted in dose-dependent vasodilation (P = 0.019), in female subjects (to approximately 44%) predominantly. The EC(50) (approximately 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.
authors.affiliation: Department of Medicine, University of California at San Diego and Veterans Affairs, San Diego Healthcare System, La Jolla, California, USA.
authors.forename: Maple M
authors.initials: MM
authors.lastname: Fung
authors.forename: Rany M
authors.initials: RM
authors.lastname: Salem
authors.forename: Parag
authors.initials: P
authors.lastname: Mehtani
authors.forename: Brenda
authors.initials: B
authors.lastname: Thomas
authors.forename: Christine F
authors.initials: CF
authors.lastname: Lu
authors.forename: Brandon
authors.initials: B
authors.lastname: Perez
authors.forename: Fangwen
authors.initials: F
authors.lastname: Rao
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ziegler
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Mahata
authors.forename: Daniel T
authors.initials: DT
authors.lastname: O'Connor
mesh_terms: D000328:Adult; D053379:Chromogranin A / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006225:Hand / Q000098:blood supply*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000494:pharmacology; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D012727:Sex Characteristics; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D053379:Chromogranin A; D010187:Pancreatic Hormones; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; C109084:chromogranin A (344-364); C050836:pancreastatin; D010656:Phenylephrine