Current Vascular Pharmacology - Volume 12, Issue 2, 2014

GPCR-mediated receptor transactivation of EGFR, is one of the effector mechanisms by which GPCR ligands, such as Ang II, thrombin and ET -1, catecholamine, SII-angiotensin, PAF, and uPA that are released at the arterial injury sites, can potentiate intimal hyperplasia. The process of EGFR transactivation can be cognate ligand-dependent or independent. In cognate ligand- dependent transactivation, ligand-bound GPCR resu Read More

The discovery of endothelin (ET) in 1988 has led to considerable effort to unravel its implication in health and disease and the mechanisms evoked by ET. ET-1 and related signaling aberrancies are believed to be implicated in the pathogenesis of diverse cardiovascular diseases, such as hypertension, atherosclerosis, hypertrophy and diabetes. The endothelin system consists of three potent vasoconstrictive isopeptides, E Read More

G-protein coupled receptors (GPCRs) are commonly present at the plasma membrane and their signaling modulates excitation-contraction coupling and excitation-secretion coupling of excitable and non-excitable cells of the cardiovascular system. Their effect on excitation-gene expression coupling was attributed, in part, to the nuclear translocation of their signaling and/or to the entry into the nuclear membrane of the inter Read More

Endogenous kinins are important vasoactive peptides whose effects are mediated by two G-Protein-coupled receptors (R), named B2R (constitutive) and B1R (inducible). They are involved in vascular homeostasis, ischemic pre- and post- conditioning, but also in cardiovascular diseases. They contribute to the therapeutic effects of angiotensin-1 converting enzyme inhibitors (ACEI) and angiotensin AT1 receptor blockers. Benefit Read More

Vasoactive peptides such as angiotensin II and endothelin-1 as well as growth factors regulate vascular homeostasis through signaling pathways that are triggered in both normal and disease states. These vasoactive peptides and growth factors also increase the cellular levels of calcium which, through calcium binding effector systems initiating the downstream signaling and physiological responses in target cells. A multif Read More

G protein signaling is an extremely complex event that is involved in almost every cellular process. As such, G protein-coupled receptors are the most commonly found type of transmembrane receptors used by cells to initiate intracellular signaling events. However, the widely accepted model of cyclical GDP-GTP exchange in response to ligand binding to 7TMRs, followed by dissociation of the G protein subunits and activation of Read More

The integrity of the vitamin D endocrine system is essential for human health. Nutritional vitamin D deficiency in otherwise healthy individuals, associates with a higher risk of mortality for all causes, despite normal serum calcitriol. These deadly causes extend beyond the recognized adverse impact of vitamin D deficiency on calcium and phosphate homeostasis predisposing to secondary hyperparathyroidism, bone lo Read More

Vitamin D is essential for maintaining a healthy mineral and bone metabolism. It stimulates calcium and phosphate absorption by the intestine, regulates bone metabolism, and negatively controls PTH secretion through the endocrine action of its active metabolite calcitriol. Vitamin D also possesses a variety of effects unrelated with mineral and bone metabolism, including the regulation of arterial blood pressure and the p Read More

In patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), 25OH-vitamin D (calcidiol) deficiency or insufficiency is a common finding with high prevalence. Numerous epidemiological studies have found an independent association of low levels of calcidiol with increased morbidity and mortality. Within different patient cohorts, application of cholecalciferol or ergocalciferol (native vitamin D) as w Read More

The synthesis of 1α,25-dihydroxyvitamin D3 (Calcitriol) takes place mostly in the kidneys through the action of 1α-hydroxylase (CYP27B1) which converts 25(OH)D into 1,25(OH)2D3. Renal production of calcitriol is stimulated by PTH, low calcium and low phosphate and it is reduced by high phosphate and FGF23. Binding of 1α,25-dihydroxyvitamin D3 to its receptor (VDR) causes gut absorption of calcium and phosphate, decr Read More

Alfacalcidol is a widely used vitamin D compound, especially in clinical nephrology because it does not require enzymatic activation by the kidneys. For that reason it has been used for decades to treat abnormalities in bone and mineral balance that arise in chronic kidney disease. In this review an overview is provided of available experimental and clinical data that form the basis of its widespread use. Supported by studies on ce Read More

Compared to such native vitamin D agents as cholecalciferol (D3), egocalciferol (D2), and calcifediol (25- hydroxy vitamin D3, which need 1-alpha hydroxylase to be activated, 1-alpha-ergocalciferol, also known as doxercalciferol, is a synthetically manufactured vitamin D analog used for treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). Doxercalciferol exhibits more structural similaritie Read More

The activation of vitamin D receptors (VDR) - (including activation by 25-hydroxyvitamin D) - seems to have not only mineral-metabolism beneficial effects but also important extra-skeletal actions. Paricalcitol is a synthetic vitamin D2 agonist of the VDR approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD). As a result of its selectivity, paricalcitol provides a wide Read More

22-oxacalcitriol (OCT) is a vitamin D3 analog and a vitamin D receptor activator (VDRA) that is used as a drug for secondary hyperparathyroidism (SHPT) and has been available clinically in Japan since 2000. The pharmacological characteristics of OCT include rapid clearance from the systemic circulation compared to that of calcitriol, good tissue distribution, and relatively long retention in the nucleus in parathyroid cells. In clini Read More

In this brief review we point out the specificities of the vitamin D system that are necessary to understand why each change in the molecule can result in significantly different biologic effects. Vitamin D, with a specific receptor in most of the tissues, has innumerable potential therapeutic applications in many clinical fields. However, excessive pharmacologic increments of circulating natural metabolites carry the risk of sig Read More

Numerous drugs with vitamin D activity are available for clinical use and it may not be easy for the nonspecialist to select the most suitable for the individual patient. In this paper we review the main characteristics of the available drugs and provide evidence about any potential specific clinical indications, with special emphasis on renal patients, in order to facilitate the optimal choice. Natural vitamin D products (i.e. those identi Read More