Reperfusion of ischemic myocardium is essential for tissue salvage but paradoxically contributes to cell death. We hypothesized that activation of potential survival pathways such as p42/p44 MAPK may prevent lethal reperfusion injury. Urocortin is a peptide factor that affects the p42/p44 MAPK signaling pathway. Both isolated and in vivo rat heart models were used to examine the potential for u...

Over the past decade, clinical development of natriuretic peptide analogues as drug therapy for acute heart failure has sparked a wide range of interests to seek other endogenous vasoactive peptide systems that are operative as adaptive responders in human heart failure. With rapid advances in the molecular understanding of heart failure pathogenesis, several novel neurohormonal systems have be...

BACKGROUND Urocortin 2 and urocortin 3 are endogenous peptides with an emerging role in cardiovascular pathophysiology. We assessed their pharmacodynamic profile and examined the role of the endothelium in mediating their vasomotor effects in vivo in man. METHODS AND RESULTS Eighteen healthy male volunteers (23±4 years) were recruited into a series of double-blind, randomized crossover studie...

Urocortin, a vasodilatory peptide related to corticotropin-releasing factor, may be an endogenous regulator of blood pressure. In vitro, rat tail arteries are relaxed by urocortin by a cAMP-mediated decrease in myofilament Ca2+ sensitivity through a still unclear mechanism. Here we show that contraction of intact mouse tail arteries induced with 42 mmol/L KCl or 0.5 micromol/L noradrenaline was...

Urocortin, a vasodilatory peptide related to corticotropin-releasing factor, may be an endogenous regulator of blood pressure. In vitro, rat tail arteries are relaxed by urocortin by a cAMP-mediated decrease in myofilament Ca sensitivity through a still unclear mechanism. Here we show that contraction of intact mouse tail arteries induced with 42 mmol/L KCl or 0.5 mol/L noradrenaline was associ...

OBJECTIVES The goal of this study was to determine the bioactivity of urocortin (Ucn) in experimental heart failure (HF). BACKGROUND Urocortin may participate in cardiovascular function and pressure/volume homeostasis. Its effects in HF are unknown. METHODS Eight normal sheep and eight sheep with pacing-induced HF received ovine Ucn (10, 50, and 100 mg intravenous boluses at 2-h intervals) ...

BACKGROUND The existence of a "placental clock" which determines the duration of gestation has been previously proposed. It is related to placental CRH secretion and is active from an early phase in human pregnancy. Urocortin is a specific ligand for the corticotropin-releasing factor (CRF) receptor expressed by human trophoblast and fetal membranes. The purpose of this study was to evaluate wh...

Urocortin, a new mammalian member of the corticotropin-releasing factor (CRF) family has been proposed to be the endogenous ligand for CRF receptor 2 (CRF-R2). We studied the influence of intravenous urocortin on gastric emptying and the role of CRF-R2 in peptide action and postoperative gastric ileus in conscious rats. The intravenous doses of rat CRF and rat urocortin producing 50% inhibition...

Corticotropin releasing factor (CRF) is known to be involved in the stress response and in some degenerative brain disorders. In addition, CRF has a role as a neuromodulator in adult cerebellar circuits. Data from developmental studies suggest a putative role for CRF as a trophic factor during cerebellar development. In this study, we investigated the trophic role for CRF family of peptides by ...