Corticotropin-releasing factor (CRF), a neuropeptide of 41 amino acids, acts as the major physiological regulator of the basal and stress-induced release of corticotropin (ACTH), beta-endorphin and other proopiomelanocortin-derived peptides from the anterior pituitary gland. In addition to its endocrine activity, CRF displays extrahypophysiotropic effects, mainly as a regulator of stress responses. We show here that CRF may additionally function as a differentiating factor in immortalized noradrenergic neuronal CATH.a cells that express CRF receptor type I and resemble locus coeruleus-derived neurons. CRF triggers morphological changes in CATH.a cells including the appearance of extended long, slender neurites with prominent growth cones. CRF-treated CATH.a cells exhibit a morphology similar to locus coeruleus neurons in primary culture. CRF-induced neurite outgrowth of CATH.a cells was blocked by addition of inhibitors for cAMP-dependent protein kinase or extracellular signal-regulated protein kinase (ERK), a subtype of the mitogen-activated protein kinases. The participation of ERK within the CRF signalling cascade was further confirmed by Western blot experiments, with antibodies directed against the phosphorylated form of ERK, and also with transcription-based assays. We conclude that CRF functions as a differentiating factor of CATH.a cells via the cAMP and the MAP kinase signalling pathways.

Abstract-Some antihypertensive agents may improve resistance artery remodeling in hypertensive patients whereas other agents may not, for similar blood pressure reduction. We questioned whether the selective mineralocorticoid receptor blocker eplerenone improves resistance artery remodeling in hypertensive patients versus the ␤-blocker atenolol. Sixteen hypertensive patients were randomly assigned to double-blind daily treatment with eplerenone or atenolol. Resistance arteries from gluteal subcutaneous tissue were assessed on a pressurized myograph. After 1 year of treatment, systolic and diastolic blood pressures were similarly well controlled in both groups. Endothelial function did not change with treatment in either group. Media/lumen ratio and cross-sectional area were unchanged in either the atenolol or the eplerenone group. In atenolol-treated patients, the arterial wall became stiffer, whereas in the eplerenone-treated patients, it became less stiff and similar to that of a normotensive control group. The media collagen/elastin ratio was reduced only after eplerenone treatment. Circulating concentrations of osteopontin, monocyte chemoattractant protein-1, basic fibroblast growth factor, interleukin-8, and interleukin-10 were significantly reduced only by eplerenone. However, plasma interleukin-1 receptor a concentration was significantly reduced by both drugs. In conclusion, in hypertensive patients, blood pressure control for 1 year with atenolol was associated with increased wall stiffness of resistance arteries, whereas eplerenone treatment was associated with reduced stiffness, decreased collagen/elastin ratio, and a reduction in circulating inflammatory mediators. These data raise the possibility that eplerenone treatment of hypertensive patients when normalizing blood pressure could potentially be associated with better vascular protection and outcomes than the ␤-blocker atenolol, which remains to be demonstrated. Key Words: aldosterone Ⅲ vascular remodeling Ⅲ extracellular matrix Ⅲ collagen Ⅲ elastin Ⅲ inflammatory biomarkers N ormalization of elevated blood pressure (BP) in hypertensive individuals is associated with reduced targetorgan damage and incident cardiovascular morbidity and mortality. 1 Small artery structural alterations may precede many clinical manifestations of end-organ damage in hypertensive patients 2 and predict the occurrence of future cardiovascular events. 3 Activation of the renin-angiotensinaldosterone system has been associated with increased cardiovascular morbidity and mortality in hypertensive patients. We and others have shown that antihypertensive drugs that interfere with the renin-angiotensin-aldosterone system exert potentially beneficial effects on vascular structure beyond BP control in hypertensive patients at variable risk for cardiovascular disease 4 -7 by improving the functional and anatomic alterations of resistance arteries typically found in experimental and human hypertension and which participate in increased peripheral resistance.Aldosterone is a mine...

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The large utilisation of ambulatory blood pressure monitoring (ABPM) highlighted several measures of BP variability. Among these, the SBP increase during awaking hours (morning surge: MS) was found to be associated to the onset of major cardiovascular events. Aim of the study was to recognise if MS, calculated in order of nocturnal minimal SBP (mNBP) or last 2 hours of sleep, as preawaking time (PAW), was characterised by a different microvascular damage during the early phases of hypertension. By diurnal (day:08.00-22.00) and nocturnal (night:24.00-06.00) ABPM, personal diary, calculation of mNBP-MS and PAW-MS, we studied 200 consecutive untreated grade-1 hypertensives, divided in patients with lower (↓) and higher (↑) MS, with similar age, metabolic features and smoking habit (see table).

Introduction: The risk for events secondary to impaired cerebral perfusion is magnified by hypertension which also shows a premature microvascular damage Aim of the study was to distinguish the progression of both the cerebral vasodilating reactivity and the microvascular damage during the very early phases of hypertension. Methods: Based on office and ambulatory blood pressure (BP) values, 22 normotensives (NTN), 18 patients with normal-high BP (NHBP) and 22 grade-1 hypertensives (HTN) males, with similar age, metabolic assessment and smoking habits, underwent trans-cranial and carotid echocolour-doppler exams. The intima-media thickness (IMT) and the PP/SVi ratio served as indices of macrovascular damage and arterial stiffness. The breath holding index (BHI), as percent change of blood flow velocity of the medial cerebral artery following apnoea, served as index of vasodilating reactivity.