ularitide and Cardiovascular-Diseases

In recent years, biomarkers have been recognized as important tools for diagnosis, risk stratification, and therapeutic decision-making in cardiovascular diseases. Currently, the clinical potential of several natriuretic peptides is under scientific investigation. The well-known counter-regulatory hormones are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), dendroaspis natriuretic peptide (DNP) and urodilatin, which play an important role in the homeostasis of body fluid volume. ANP and BNP have already been demonstrated to have diagnostic usefulness in a great number of studies, which have progressed from bench to bedside. This article summarizes existing data on ANP and related peptides in cardiovascular and other disorders, and outlines the potential clinical usefulness of these markers.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Elapid Venoms; Homeostasis; Humans; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Peptide Fragments; Peptides

Thus far, five molecules comprise the natriuretic peptide family (NPF): ANP, urodilatin, BNP, CNP and DNP. Precursor hormones for ANP, BNP and CNP are encoded by a different gene. Final peptides are ligands for A, B and C receptors, acting the latter as a clearance receptor besides neutral endopeptidase (EC 24.11). cGMP acts as a second messenger. Natriuretic peptides (NP) have well-known functions such as natriuretic, antihypertensive and reduction of plasma renin-aldosterone concentrations. An antiinflammatory ANP potential and a pro-apoptotic action in rats endothelial cells of different NP have been described. Unlike adults, NP show a different distribution during ontogeny and a different pattern of excretion under different stimuli. Noncompetitive immunoassays have become more suitable than competitive ones for routine measurement of NP with recent advances in speed of measurement. BNP and pro-BNP are emerging as useful tools in diagnosis, management and prognosis of heart disease. Preliminary data support a role of NP in the therapy of congestive heart failure. Finally, potential therapeutic compounds of NP in different pathologies are updated with an important focus on vasopeptidase inhibitors. These are capable of strengthening NP and inhibiting renin-angiotensin system at the same time, as potential useful molecules in cardiovascular therapy.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Humans; Molecular Sequence Data; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Peptide Fragments

In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis.. In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course.. Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data.. In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number, NCT01661634 .).

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Diuretics; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Hypotension; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Aim was to compare the effects of estradiol-only therapy with combined estradiol/progestin treatment on the excretion of vasoactive mediators surrogating on possible effects in the vascular system. The progestin used was dienogest, a new C19-progestin with antiandrogenic properties.. Prospective, randomized trial, 25 healthy postmenopausal women treated for 3 months with estradiol valerate (2 mg/day) and 27 women with estradiol valerate (2 mg/day) continuously combined with dienogest (2 mg/day). Assessment of the following markers or their stable metabolites in nocturnal urine: cGMP, serotonin, prostacyclin and thromboxane, and urodilatin.. Estradiol alone increased the excretion of cGMP and serotonin significantly suggesting vasodilating effects. The prostacyclin/thromboxane ratio known to be crucial for the relation of vasorelaxation to vasoconstriction significantly increased. No significant changes were found for urodilatin, which is known to elicit different effects in the cardiovascular and renal system, respectively. Combined estradiol/dienogest therapy also led to significant increases in cGMP and serotonin excretion suggesting that progestin addition for three months does not affect these markers. However, in contrast to estrogen-only treatment, there was no significant increase for the prostacyclin/thromboxane ratio, which can be explained by antagonistic action of the progestin. The excretion of urodilatin was increased significantly, which might be due to counterbalancing progestin effects in the renal vascular system.. The changes in vasoactive markers suggest an estrogen effect that is vasorelaxant. Since there were no significant differences between the two groups, possible vascular effects of the progestin dienogest, for the first time evaluated, might not be of clinical relevance, at least not in women without cardiovascular diseases.

Topics: Administration, Oral; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Cyclic GMP; Estradiol; Female; Hormone Replacement Therapy; Humans; Middle Aged; Nandrolone; Peptide Fragments; Postmenopause; Prospective Studies; Serotonin; Vasodilation

Ularitide is a member of the natriuretic peptide family. This hormone exhibits an N-terminal extension by four amino acids compared with atrial natriuretic peptide. Ularitide was shown to exert strong diuretic and natriuretic effects when infused intravenously. Its main action sites are the glomerulum, inducing preglomerular vasodilation and postglomerular vasoconstriction and thereby elevating the glomerular filtration rate, and the tubular system inhibiting Na(+)-reabsorption. In initial uncontrolled clinical trials, this peptide was shown to have beneficial effects in patients suffering from oliguric acute renal failure.. We conducted a double-blind, placebo-controlled, multicenter, dose-finding trial recruiting 176 patients randomized into 4 different Ularitide doses groups (U5, U20, U40, and U80 ng/kg/min) and a placebo group (U0). Ularitide/placebo infusion was performed for 5 days with half the originally infused dose on day 5. The primary objective of the study was to test various doses of Ularitide in patients suffering from oliguric acute renal failure to avoid mechanical renal replacement therapy during the first 12 hours.. The results indicate that Ularitide does not reduce the incidence of mechanical renal replacement therapy compared with placebo-treated patients during the first 12 h of treatment (U0: 36 (20), U5: 35 (11), U20: 36 (9), U40: 28 (8), U80: 41 (12), (% (n) (p = 0.87)). Diuresis increased in the Ularitide-treated groups and the placebo group after onset of infusion and did not show any significant difference in the first 12 h collection period (U0: 576, U5: 514, U20: 500, U40: 360, U80: 158 ML/12h (Median), (p = 0.16)).. In summary, the incidence of mechanical renal replacement therapy in critically ill patients suffering from oliguric acute renal failure could not be altered positively by Ularitide administration according to our protocol. Further prospective clinical trials are needed to answer the question whether a different patient collective or a prophylactic administration of Ularitide are more promising approaches in the clinical setting of oliguric acute renal failure.

Topics: Acute Kidney Injury; Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Urea Nitrogen; Cardiovascular Diseases; Creatinine; Diuretics; Double-Blind Method; Female; Humans; Hypotension; Male; Middle Aged; Peptide Fragments; Renal Replacement Therapy; Time Factors