Search results for "Endothelins"
showing 10 items of 30 documents
Safety and Ergogenic Properties of Combined Aminophylline and Ambrisentan in Hypoxia.
2017
We hypothesized that concomitant pharmacological inhibition of the endothelin and adenosine pathway is safe and improves exercise performance in hypoxic humans, via a mechanism that does not involve augmentation of blood oxygenation. To test this hypothesis, we established safety and drug interactions for aminophylline (500 mg) plus ambrisentan (5 mg) in normoxic volunteers. Subsequently, a placebo‐controlled study was employed to test the combination in healthy resting and exercising volunteers at simulated altitude (4,267 m). No serious adverse events occurred. Drug interaction was minimal or absent. Aminophylline alleviated hypoxia‐induced headaches. Aminophylline, ambrisentan, and their…
Central obesity and hypertensionThe role of plasma endothelin
1996
Hypertension and central obesity are two conditions closely linked, but the mechanisms responsible for obesity-associated hypertension are still unclear. In the last few years, several studies addressed the role of endothelin-1 (ET-1) in the development and maintenance of hypertension. This study was designed to evaluate plasma ET-1 in normotensive and hypertensive central obese subjects compared with a lean healthy group. Our final goal was to analyze the relationship between plasma ET-1, blood pressure, and left ventricular structure and function in central obese subjects (both normotensives and hypertensives). ET-levels have been assessed by the radioimmunoassay method in 20 lean normote…
Endothelium-derived factors in microalbuminuric and nonmicroalbuminuric essential hypertensives
2000
Previous evidence has demonstrated a relationship between growth factors and cardiovascular diseases. This study was aimed at evaluating levels of some endothelium-derived growth factors, and their relationship with microalbuminuria (MAU), in essential hypertension. Ninety-nine mild-moderate essential hypertensives (EH) and 25 healthy controls were studied. All patients underwent 24-h blood pressure monitoring, serum endothelin-1 (ET-1), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), and 24-h MAU assays. Later, EH were divided into two subsets consisting of microalbuminurics (MAU >11 microg/min) and nonmicroalbuminurics (MAU <11 microg/min). In microalbumin…
Role of endothelium and calcium channels in endothelin-induced contraction of human cerebral arteries
1990
Endothelin constricted human isolated cerebral arteries in a concentration-dependent manner. The maximal tension developed, as well as EC50 values were similar in arteries with and without endothelium. Removal of extracellular calcium or addition of the calcium antagonist nicardipine (10(-6)M), attenuated but did not abolish responses to endothelin. These experiments show that the endothelin-induced contraction in human cerebral arteries is not linked to the presence of intact endothelial cells. The data also show that the contractile effects of endothelin cannot be explained solely by an action on voltage-dependent calcium channels.
Contractile Response of Human Omental Arteries to Endothelin
1992
Abstract The effects of endothelin have been studied in isolated arterial segments (0·8–1 mm in external diam.) of human omental arteries obtained during the course of abdominal operations (15 patients, 7 men and 8 women). Paired segments, one normal and the other de-endothelized, were mounted for isometric recording of tension in organ baths. Endothelin produced concentration-dependent contractions with an EC50 value of 5·4 × 10−9 m. Removal of endothelium did not affect significantly endothelin-induced contractions (EC50, 6·7 × 10−9 m). Removal of extracellular calcium or addition of the calcium channel blocker nicardipine (10−6 m) diminished but did not abolish responses to endothelin…
In vivo relationship between insulin and endothelin role of insulin-resistance
1997
Since endothelin production is stimulated in vitro by insulin, we performed this study to evaluate in vivo the relationships between endothelin and insulin plasma levels during a glucose load. We studied 28 subjects; 17 with normal glucose tolerance (NGT) and 11 with impaired glucose tolerance (IGT). Ten of the subjects in this study were normotensive and 18 with mild to moderate hypertension. Age, sex and body mass index were comparable among the groups. After a 2-week period of washout they underwent an oral glucose tolerance test; blood was drawn at 0 (basal), 90 and 120 min after the load for determination of glucose, insulin, C-peptide of insulin and endothelin-1 and -2. Basal endothel…
Endothelin receptors mediating contraction in goat cerebral arteries
1993
1. The aim of the present study was to identify the subtype of receptor mediating contraction to endothelin-1 and sarafotoxin S6b in goat isolated middle cerebral arteries. 2. Endothelin-1, endothelin-2 and endothelin-3 contracted cerebral arteries in a concentration-dependent manner. Although the three peptides were full agonists, the order of potency was endothelin-1 = endothelin-2 > endothelin-3, with a relative potency of endothelin-1 and endothelin-2 versus endothelin-3 of approximately 280. Sarafotoxin S6b induced concentration-dependent contractions with lower potency than endothelin-1/endothelin-2, higher potency than endothelin-3 and a higher maximum response than the three endothe…
Subtype-Specific Desensitization of Human Endothelin ETA and ETB Receptors Reflects Differential Receptor Phosphorylation
1997
Endothelins regulate blood pressure in mammals through G protein-coupled receptors. Two receptor subtypes, ETA and ETB, exist which differ by their agonist profiles. Here we show subtype-specific differences in the inactivation of these endothelin receptors. Using a modified inositol phosphate accumulation assay, we found that stimulation of ETA by endothelin-1 results in sustained activation of the subtype, retaining >30% of its initial activity even 20 min after agonist administration, whereas the ETB rapidly deactivated after agonist stimulation, losing >80% of its initial activity within 5 min after endothelin application. The discrepancy in receptor inactivation is reflected by subtype…
Isolation of the Endothelin B Receptor from Bovine Lung Structure, Signal Sequence, and Binding Site
1995
Bovine lung endothelin-B receptor has been isolated in good yield with a new procedure involving the use of endothelin-1 coupled to iminobiotin with a long spacer and avidin-agarose affinity chromatography. Contrary to previous reports, evidence has been obtained that the native form of this receptor corresponds to the full-length transcript expected on the basis of cDNA clones. The binding of endothelin to a variety of shortened fragments of the full receptor suggests that the long N-terminal sequence of this receptor has very little influence on the binding of endothelin and that the main determinants of the endothelin binding site might be constituted by residues in the sixth, and possib…
Endothelin: an endothelium-derived vasoactive peptide and its possible role in the pathogenesis of cerebral vasospasm
1991
The contractile response to endothelin has been examined in cerebral arteries from rats subjected to a prior subarachnoid haemorrhage (SAH) and compared with saline injected controls. Endothelin elicited strong concentration-dependent contraction of rat basilar artery segments. The response was slow in onset and long lasting. The endothelin-induced contraction was much stronger in the SAH compared to control animals. Our findings suggest a role of the peptide in the pathophysiology of cerebral vasospasm.