Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 446

Adrenomedullin has many effects. It regulates cellular growth and differentia-
tion. It impedes the secretion of ACTH, aldosterone, and cortisol. It is involved in
the regulation of fluid and electrolyte balance (diuresis and natriuresis). Adreno-
medullin also enhances cardiac contractility (inotropic effect).
In isolated porcine ciliary arteries, adrenomedullin induces arterial relaxation
via CGRP 1 receptors. This vasodilation can be mediated either by the release of
EDHF and NO and activation of calcium- and ATP-dependent K + channels or be
independent of NO and EDHF [ 827 ].
ADP, ATP, Acetylcholine, and Substance-P
Endothelial cells synthesize the vasodilator acetylcholine [ 828 ]. Fluid flow releases
of adenosine triphosphate , acetylcholine, and substance-P from cultured endothelial
cells [ 829 ].
Adenosine diphosphate , a P2Y ligand, produces vasodilation. Endothelial P2X 4
channels are strongly involved in flow-sensitive mechanisms that regulate local
blood pressure and vascular remodeling [ 830 ].
Substance-P is a vasodilator that activates nitric oxide synthase and releases
nitric oxide from the endothelium. It also acts as a neurotransmitter and modulator.
It belongs with neurokinin-A 79 and -B to the tachykinin neuropeptide family,
members of which bind to 3 known G-protein-coupled receptors (NK 1 -NK 3 )that
activate phospholipase-C.
Ghrelin
Ghrelin is the endogenous peptide ligand for the ghrelin receptor (a.k.a. growth
hormone secretagogue receptor GHSR1a). In humans, it is a potent vasodilator.
It exerts a direct effect on vascular smooth myocytes, with a potency comparable
to that of natriuretic peptides [ 812 ].
Ghrelin is secreted by parietal oxyntic cells of the stomach epithelium and
circulates at relatively high concentrations. Ghrelin is also detected in endothelial
cells throughout the human vasculature, where it can act as an endothelium-derived
vasoactive peptide.
Relaxin
Relaxin, a heterodimeric peptide hormone produced from prorelaxin, is a renal
vasodilator. It favors angiogenesis. Relaxin relaxes the uterine musculature. It
inhibits collagen synthesis and enhances matrix metallopeptidase activity. Relaxin
79 Neurokinin-A is also called substance-K. Neurokinin-A mediates contraction of the colon.