Direct Vasoactive Effects of the Chromogranin A (CHGA) Peptide Catestatin in HumansIn 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 ~ 50, ~ 500, ~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 ~ 69%, increasing concentrations of catestatin resulted in dose-dependent vasodilation (P = 0.019), in female subjects (to ~ 44%) predominantly. The EC50 (~ 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.

Catestatin reduces myocardial ischaemia/reperfusion injury: involvement of PI3K/Akt, PKCs, mitochondrial KATP channels and ROS signalling

“…CST also caused vasodilatation in human subjects with a NO-dependent mechanism [16]. Recently, on the isolated rat heart, CST was found to elicit a vasorelaxant influence on coronary arteries pre-contracted by endothelin-1, together with negative inotropic and lusitropic actions, counteracting the positive effects elicited by the β-adrenoceptor activator, isoproterenol [3].…”

“…Actually, CST is known to counteract exaggerated β-adrenergic activity, which is relevant part of the neuroendocrine scenario of heart failure [1][2][3][4], and to dilate human vessels in vivo [16], thus exerting positive effects on cardiac afterload. In line with these evidences and since β-blockade is largely used as post-ischaemic treatment, the present work suggests that exogenous CST may provide new tool for pharmacological postconditioning.…”

Catestatin has an unexpected effect on the intrathecal actions of PACAP dramatically reducing blood pressure

“…Catestatin exerts divergent actions depending on the tissue being investigated (23,30,34). In the periphery, catestatin causes vasodilation (11) and has antimicrobial actions in the human epidermis, suggesting a role for catestatin in the cutaneous defense system (47). In the brain stem, it is sympathoexcitatory and enhances sympathetic barosensitivity (13).…”

“…Catestatin is contained within 88% of C1 RVLM neurons, and PACAP-38 is expressed in 85% of bulbospinal C1 RVLM neurons, indicating extensive colocalization of these neurotransmitters in this nucleus (9, 13). The separate effects of these peptides have been studied following injection into the intrathecal space and into the RVLM, (9,12,49,50), but the physiological significance of this extensive colocalization is unclear.Catestatin and PACAP are both vasodilator peptides in the periphery (11,54). Intrathecal PACAP increases splanchnic sympathetic nerve activity (sSNA) and heart rate (HR) but does not affect mean arterial blood pressure (MAP) (9).…”

“…Catestatin and PACAP are both vasodilator peptides in the periphery (11,54). Intrathecal PACAP increases splanchnic sympathetic nerve activity (sSNA) and heart rate (HR) but does not affect mean arterial blood pressure (MAP) (9).…”