endothelin-1 and Constriction--Pathologic

Since endothelial dysfunction may significantly contribute to the pathophysiology of hypertension and its complications, its modification seems to be a very attractive means to favourably affect the development of atherosclerosis and cardiovascular events in hypertensive patients. However, not all antihypertensive drugs consistently improve endothelial dysfunction. While first-generation beta-blockers showed contrasting or null effects on endothelial function, newer beta-blockers of the third generation, such as carvedilol and nebivolol, seem to be provided with specific endothelium-mediated vasodilating effects. Calcium channel blockers are generally able to increase endothelium-dependent vasodilation in several vascular beds, in patients with essential hypertension, probably through multiple mechanisms. Most studies have shown thatACE inhibitors favourably affect endothelial function mainly in the subcutaneous, epicardial and renal circulation, not only by inhibiting the effects of angiotensin II on the endothelium, but also by enhancing bradykinin-induced vasodilation, probably a hyperpolarization-related effect. On the other hand, discordant evidence is available about the effects of angiotensin II receptor type I blockers on endothelial function in patients with essential hypertension, atherosclerosis or diabetes.There are data suggesting that an increased activity of the endothelin- I system may play a role in the blunted endothelium-dependent vasorelaxation of hypertensive patients, an effect that could be contrasted by the use of endothelin-I receptor antagonists. However, to date no substantial clinical efficacy of endothelin-I receptor blockers has been shown in patients with essential hypertension. Finally, other possibly useful compounds in restoring impaired endothelial function in hypertension are some antioxidant agents such as vitamin C, folic acid, the cofactor tetrahydrobiopterin (BH4), L-arginine and the drugs of the statin class.

Topics: Animals; Antihypertensive Agents; Arteriosclerosis; Constriction, Pathologic; Endothelin-1; Endothelium, Vascular; Humans; Hypertension; Vasodilation

Oxygen supplementation is regularly prescribed to patients to treat or prevent hypoxia. However, excess oxygenation can lead to reduced cerebral blood flow (CBF) in healthy subjects and worsen the neurological outcome of critically ill patients. Most studies on the vascular effects of hyperoxia focus on arteries but there is no research on the effects on cerebral capillary pericytes, which are major regulators of CBF. Here, we used bright-field imaging of cerebral capillaries and modeling of CBF to show that hyperoxia (95% superfused O

Topics: Calcium; Capillaries; Cerebrovascular Circulation; Constriction; Constriction, Pathologic; Endothelin-1; Humans; Hyperoxia; Oxygen; Pericytes; Reactive Oxygen Species

Cerebral blood flow is reduced early in the onset of Alzheimer's disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism. We found that in humans with cognitive decline, amyloid β (Aβ) constricts brain capillaries at pericyte locations. This was caused by Aβ generating reactive oxygen species, which evoked the release of endothelin-1 (ET) that activated pericyte ET

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Biopsy; Capillaries; Cerebral Cortex; Cerebrovascular Circulation; Constriction, Pathologic; Endothelin-1; Humans; Hypoxia; Mice; Pericytes; Protein Multimerization; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptor, Endothelin A; Signal Transduction; Vascular Resistance

Congenital hydronephrosis is induced by congenital obstruction of uretero pelvic junction, bladder vesicoureteral reflux, posterior urethral valve, stricture of ureter end and ureterocyst, which is extremely apt to cause end-stage renal failure in children. It becomes significant to explore the expression profile and clinical significance of aquaporin-1 (AQP-1) and ET-1 (endothelin-1) in the urine of children with congenital hydronephrosis.. 80 cases of children with congenital hydronephrosis were selected to be the observation group and another 40 cases of children with other diseases were served as control group. Pre-operative morning urine, intra-operative renal pelvis urine and morning urine at the 7th day after the operation of all the children were collected for the detection of the level of ET-1, Cr level and AQP1 in the urine. Urine various indexes of different diseases stages in children of both groups were compared.. There was no significant difference between children with mild and children in control group (p > 0.05). In the observation group, the AQP-1 level during the operation was significantly lower than that before operation, but it was significantly higher in post-operation than that during the operation, which was still lower than that in control group (p < 0.05). Urine ET-1 level in observation group and its positive rate were significantly higher than that in control group (p < 0.05). Serum stress indexes in each stage of the observation group were significantly higher than that in control group (p < 0.05).. The expression levels of urine AQP-1 and ET-1 of children with congenital hydronephrosis were obviously increased. The AQP-1 level during the operation was lower than that before operation. This post-operation level was significantly higher than before the operation. The expression of AQP-1 and ET-1 could be used as important indexes for clinical diagnosis.

Topics: Aquaporin 1; Case-Control Studies; Child, Preschool; Constriction, Pathologic; Endothelin-1; Female; Humans; Hydronephrosis; Infant; Kidney Pelvis; Male; Postoperative Period; Ureter; Vesico-Ureteral Reflux

The aim of the present study was to examine cerebral vasoconstriction in patients with chronic high altitude disease [cerebrovascular reactivity (CVR)], and to evaluate differences in alterations of brain vascular contractile reactivity of chronic mountain sickness (CMS) patients and healthy controls. Alterations of endothelin (ET) and its receptor, as well as endothelial nitric oxide synthase (eNOS) levels in the plasma were examined to determine the cerebral reservation capacities in CMS patients. Transcranial Doppler ultrasound and carbon dioxide analysis methods were used to detect the CVR variances. At the same time, enzyme‑linked immunosorbent assay approaches were utilized to detect the ET and ET B receptor and the eNOS levels in serum of the CMS patients and healthy controls. CVR and CVRI levels in CMS patients were lower than those of the healthy control subjects and the difference was statistically significant (P<0.05). By contrast, eNOS and ET‑1 levels were not statistically significant for CMS and healthy controls (P>0.05). However, the ET receptor concentration level was higher in CMS than the healthy controls. Thus, ET‑1 may not be a direct etiological variation but may play compensatory roles in CMS patients. The results of the study may provide scientific clues for the prevention and treatment of CMS with higher blood coagulation states of cerebral infarction in patients with chronic high altitude disease.

Topics: Adult; Altitude Sickness; Biomarkers; Blood Pressure; Case-Control Studies; Cerebral Arteries; Constriction, Pathologic; Endothelin-1; Female; Heart Rate; Humans; Male; Middle Aged; Nitric Oxide Synthase Type III; Receptor, Endothelin B; Vasoconstriction; Young Adult

Our previous study reveals that total rough extract of Radix Scrophulariae has a beneficial effect on ventricular remodeling.. After carrying out a series of preliminary experiments, we speculated that angoroside C may be the effective agent.. After oral administration, the effect of angoroside C on ventricular remodeling was evaluated by using a pressure-overloaded rat model, some related indexes were detected in vivo.. A model of pressure overloaded ventricular remodeling was produced by abdominal aortic constriction (AAC) in rats. The sham-operated rats underwent an identical surgical procedure except for AAC. AAC rats were randomly divided into five groups: model control group, three angoroside C treated groups (7.5, 15 and 30 mg·kg(-1)) and captopril treated group (40 mg·kg(-1)). The rats were orally administered with the corresponding drugs or drinking water for 4 weeks. The levels of blood pressure (BP), left ventricular weight index (LVWI) and heart weight index (HWI) were detected. Myocardium tissue was stained with hematoxylin and eosin or picric acid/sirius red for cardiomyocyte cross-section area or collagen content measurements respectively. The concentrations of angiotensin Ⅱ (Ang Ⅱ), hydroxyproline (Hyp), matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in myocardium or serum were determined. Real-time RT-PCR was performed to detect the mRNA expressions of endothelin 1 (ET-1), transforming growth factor β1 (TGF-β1).. Angoroside C significantly reduced the BP, LVWI and HWI, decreased the content of Ang Ⅱ, Hyp, diminished cross sectional area of cardiomyocytes and ameliorated collagen deposition. Additionally, it markedly reduced collagen I and III expressions and regulated matrix metalloproteinase-2, 9 and inhibitors of metalloproteinase expressions. Angoroside C also down regulated the gene expressions of ET-1 and TGF-β1mRNA in myocardium.. Angoroside C has beneficial effects against ventricular remodeling. The mechanism is likely to be related to decreasing the level of Ang Ⅱ, attenuating the mRNA expressions of ET-1 and TGF-β1.

Topics: Angiotensin II; Animals; Aorta; Blood Pressure; Captopril; Collagen; Constriction, Pathologic; Coumaric Acids; Disease Models, Animal; Endothelin-1; Heart; Heart Rate; Hydroxyproline; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Scrophularia; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta1; Trisaccharides; Ventricular Remodeling

While calreticulin has been shown to be critical for cardiac development, its role in cardiac pathology is unclear. Previous studies have shown the detrimental effects on the heart of sustained germline calreticulin overexpression, yet without calreticulin, the heart does not develop normally. Thus, carefully balanced calreticulin levels are required for the heart to develop and to function properly into adulthood. But what happens to calreticulin levels, and how is this regulated, during cardiac hypertrophy, during which the fetal gene program is reactivated, at least partially? Our working hypothesis was that c-Src, a kinase whose activity we previously found to be correlated with calreticulin expression, was involved with calreticulin in regulating the response to hypertrophic signals. Thus, we subjected adult mice to transverse aortic constriction to induce left ventricular hypertrophy. We found that aortic constriction caused calreticulin levels to increase, whereas those of c-Src fell with longer constriction time. We also examined the ability of embryonic stem cell-derived cardiomyocytes to respond to soluble hypertrophic agonists. Endothelin-1 treatment caused a significantly greater cell area increase of calreticulin-null cardiomyocytes, which had higher c-Src activity, compared with wild-type cells. c-Src inhibition abolished this difference. Greater c-Src activity may explain the efficacy with which calreticulin-null cells are able to induce the hypertrophic program, while cells containing calreticulin may be able to attenuate the hypertrophic response as a result of decreased c-Src activity. Thus, calreticulin may have a protective effect on the heart in the face of cardiac hypertrophy.

Topics: Animals; Aorta; Calreticulin; Cardiomegaly; Constriction, Pathologic; Embryo, Mammalian; Endothelin-1; Gene Expression Regulation; Heart Ventricles; Hemodynamics; Hypertrophy, Left Ventricular; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Organ Size; Phenylephrine; Pressure; Signal Transduction; Solubility; src-Family Kinases

Cerebral aneurysms and arteriovenous malformations (AVM) are a common cause of stroke and cerebral hemorrage. Both are often discovered when they rupture, causing subarachnoid hemorrhage (SAH). SAH-induced vasospasm is mediated by enhanced vasoconstriction due to endothelin-1 (ET-1). We investigated whether endothelial cells (ECs) obtained from aneurysm and AVM express phenotypic and genotypic alterations contributing to the development of vasospasm after SAH. We isolated ECs from human AVM and aneurysm and then confirmed their EC origin by polymerase chain reaction and immunocytochemistry with endothelial markers. Experiments were also carried out with human cerebral microvascular and umbilical vein ECs (HCECs and HUVECs respectively) for comparison. We tested EC proliferation ability and microtubule formation in Matrigel at different cell passages. Five aneurysm (3 ruptured, 2 unruptured) and 3 AVM (2 ruptured, 1 unruptured) ECs were tested for ET-1 release in the culture medium. Aneurysm and AVM ECs expressed von Willebrand factor, Adrenomedullin, and exhibited a progressive reduction of proliferation and in vitro angiogenic ability after the V passage. Significantly higher levels of ET-1 have been detected in ECs from ruptured aneurysms and AVMs. We report the first successful isolation and characterization of primary EC lines from human cerebral vascular lesions. Augmented release of ET-1 is correlated with the rupture of the abnormal vessel confirming its role in vasospasm after SAH. Furthermore, ECs obtained from these vascular malformations can be used as an experimental model to study SAH-induced vasoconstriction.

Topics: Adrenomedullin; Cell Line; Constriction, Pathologic; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Humans; Intracranial Aneurysm; Intracranial Arteriovenous Malformations; Protein Transport; RNA, Messenger; Rupture, Spontaneous; Subarachnoid Hemorrhage; von Willebrand Factor

The purpose of this study was to explore the role of endothelin in neuropathic pain. Endothelins (ET) are a family (ET-1, ET-2, ET-3) of ubiquitously expressed peptides involved in control of vascular tone. Injected ET-1 causes intense pain via activation of ETA receptors, modulated by analgesic signals initiated by ETB receptor activation. Using a rat model of chronic constriction injury of the sciatic nerve, we found that pharmacologic ETA receptor antagonism acutely and significantly reduced thermal and mechanical hyperalgesic responses 5 days after injury. Furthermore, ET-1 and the ETA receptor are locally upregulated at the site of chronic constriction injury at both the message and the protein levels, suggesting that ET-1 may be involved in establishing pain after the injury. These data point to ET-1 as an important mediator of pain in general and suggest that ETA antagonism deserves study as a potential novel therapy for neuropathic pain.

Topics: Animals; Constriction, Pathologic; Endothelin A Receptor Antagonists; Endothelin-1; Male; Pain; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Sciatic Neuropathy

To investigate the expression of endothelin-1 (ET-1) and adrenomedullin (ADM) in the renal pelvis, stenotic ureteropelvic junction, and ureter of 20 male Wistar rats with congenital unilateral ureteropelvic junction obstruction; the normal contralateral kidneys served as controls. The molecular pathophysiology of congenital ureteropelvic junction obstruction is still unclear. The implication of altered peptidergic innervation is under discussion. Our study group has recently been able to demonstrate a significant increase in ET-1 and a significant decrease in ADM in prestenotic and stenotic tissue, but not in the remainder of the ureter, compared with controls.. Twenty animals were killed, and samples of the renal pelvis, ureteropelvic junction, upper ureter, middle part of the ureter, and lower ureter were immediately snap-frozen and stored in liquid nitrogen. Total RNA was extracted, and subsequently 1 microg of RNA was reversely transcribed. mRNA expression of ET-1 and ADM was determined semiquantitatively using on-line polymerase chain reaction. The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was determined to relate the specific mRNA expression to the expression of a housekeeping gene.. We found a significant increase in the expression of ET-1 in the obstructed junctions related to GAPDH (P <0.001). The expression of ADM, however, revealed no statistically significant differences. No differences at all could be detected in the tissue samples from the rest of the ureter.. Alterations in the local production of peptidergic neurotransmitters, especially ET-1, may contribute to the molecular pathogenesis of ureteropelvic junction obstruction. Results previously obtained in the stenotic tissue from children were confirmed in the stenotic tissue from the rat model. We hypothesize that the alterations are disease-, but not age-specific.

Topics: Abnormalities, Multiple; Adrenomedullin; Animals; Atrophy; Computer Systems; Constriction, Pathologic; Disease Models, Animal; Endothelin-1; Gene Expression Profiling; Hydronephrosis; Kidney Pelvis; Male; Peptides; Polymerase Chain Reaction; Rats; Rats, Mutant Strains; Rats, Wistar; RNA, Messenger; Ureter; Ureteral Obstruction

The lack of a cardioprotective effect of hormone replacement therapy (HRT), as suggested by the Heart and Estrogen/progestin Replacement Study (HERS) and Women's Health Initiative (WHI) may in part be explained by the progestin used. The aim of this study was to elucidate the effect of different progestins on cerebrovascular reactivity in an animal model.. Fifty-six ovariectomized New Zealand White rabbits were randomized into seven groups receiving hormone treatment for 4 weeks: medroxyprogesterone acetate (MPA) (10 mg/day); norethisterone acetate (NETA) (3 mg/day); conjugated equine estrogens (CEE) (1.25 mg/day); 17beta-estradiol (E2) (4 mg/day); MPA + CEE (10 mg/day + 1.25 mg/day); NETA + E2 (3 mg/day + 4 mg/day); or placebo. Segments from the basilar and posterior cerebral arteries were mounted in myographs for tension recordings. Concentration-response curves to potassium, acetylcholine, sodium nitroprusside, L-NAME (N(omega)-nitro-L-arginine methyl ester), calcium and endothelin-1 were established.. Treatment with MPA caused a significant increase in vasoconstriction, expressed as E(max) (mN/mm, mean +/- SEM; p < 0.05), in response to potassium (3.18 +/- 0.19 vs. 2.47 +/- 0.19) and calcium (4.00 +/- 0.22 vs. 3.34 +/- 0.14) in the posterior cerebral artery, and to endothelin-1 (6.88 +/- 0.69 vs. 5.22 +/- 0.30) in the basilar artery, when compared with NETA. This difference was neutralized in the groups receiving the combined treatment of MPA + CEE and NETA + E2. No overall differences were seen between CEE and E2.. In rabbit cerebral arteries, MPA treatment causes a higher development in arterial tension compared with NETA, indicating that different progestins may display different cerebrovascular effects. However, when accompanied by estrogens, as in the case of HRT, this difference is eliminated.

Topics: Acetylcholine; Animals; Calcium; Cerebral Arteries; Constriction, Pathologic; Contraceptive Agents, Female; Endometrium; Endothelin-1; Enzyme Inhibitors; Estradiol; Estrogens; Estrogens, Conjugated (USP); Female; Medroxyprogesterone Acetate; Models, Animal; NG-Nitroarginine Methyl Ester; Nitric Oxide Donors; Nitroprusside; Norethindrone; Norethindrone Acetate; Ovariectomy; Potassium; Rabbits; Random Allocation; Vasodilator Agents

Recent studies indicate that cardiac T-type Ca2+ current (ICaT) reappears in hypertrophied ventricular cells. The aim of this study was to investigate the role of angiotensin II (Ang II), a major inducer of cardiac hypertrophy, in the reexpression of T-type channel in left ventricular hypertrophied myocytes. We induced cardiac hypertrophy in rats by abdominal aorta stenosis for 12 weeks and thereafter animals were treated for 2 weeks with losartan (12 mg/kg per day), an antagonist of type 1 Ang II receptors (AT1). In hypertrophied myocytes, we showed that the reexpressed ICaT is generated by the CaV3.1 and CaV3.2 subunits. After losartan treatment, ICaT density decreased from 0.40+/-0.05 pA/pF (n=26) to 0.20+/-0.03 pA/pF (n=27, P<0.01), affecting CaV3.1- and CaV3.2-related currents. The amount of CaV3.1 mRNA increased during hypertrophy and retrieved its nonhypertrophic level after losartan treatment, whereas the amount of CaV3.2 mRNA was unaffected by stenosis. In cultured newborn ventricular cells, chronic Ang II application (0.1 micromol/L) also increased ICaT density and CaV3.1 mRNA amount. UO126, a mitogen-activated protein kinase kinase-1/2 (MEK1/2) inhibitor, reduced Ang II-increased ICaT density and CaV3.1 mRNA amount. Bosentan, an endothelin (ET) receptor antagonist, reduced Ang II-increased ICaT density without affecting the amount of CaV3.1 mRNA. Finally, cotreatment with bosentan and UO126 abolished the Ang II-increased ICaT density. Our results show that AT1-activated MEK pathway and autocrine ET-activated independent MEK pathway upregulate T-type channel expression. Ang II-increased of ICaT density observed in hypertrophied myocytes may play a role in the pathogenesis of Ca2+ overload and arrhythmias seen in cardiac pathology.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Animals, Newborn; Bosentan; Butadienes; Calcium Channels, T-Type; Calcium-Calmodulin-Dependent Protein Kinases; Cardiomegaly; Constriction, Pathologic; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Endothelin-1; Enzyme Inhibitors; Flavonoids; Gene Expression; Losartan; Male; Membrane Potentials; Mitogen-Activated Protein Kinase Kinases; Myocytes, Cardiac; Nickel; Nitriles; Oligopeptides; Peptides, Cyclic; Piperidines; Rats; Rats, Wistar; Receptors, Angiotensin; Receptors, Endothelin; RNA, Messenger; Signal Transduction; Sulfonamides

The pathological role of oxidative stress in patients treated by hemodialysis has gained increasing recognition in recent years. Because complications related to vascular access are a major source of morbidity, immunohistochemical evidence of oxidative stress and activation of growth factors were examined in native arteriovenous (AV) fistulae (n = 11) and expanded polytetrafluoroethylene (ePTFE) grafts (n = 15) recovered from hemodialysis patients at the time of surgical revision or resection. To show the presence of oxidative stress in tissues, three markers were chosen: N(epsilon)(carboxymethyl)lysine, a structurally identified advanced glycation end product; 4-hydroxy-2,3-nonenol, a lipid peroxidation product; and redox-active transition metals bound to proteins, a source of Fenton chemistry-generated free radicals. Markers of cell growth and proliferation were endothelin-1 (ET-1), a potent mitogenic peptide implicated in the formation of intimal hyperplasia; transforming growth factor-beta (TGF-beta), a stimulus to vascular cell growth and matrix production; and platelet-derived growth factor (PDGF), a mediator of intimal hyperplasia. All specimens studied showed significant intimal hyperplasia. In general, the neointima close to the vascular lumen of the AV fistula and the pseudointima close to the lumen of the ePTFE graft were positive for oxidative stress markers. At sites of injury, especially in the presence of histological evidence of inflammation and healing, expression of oxidative markers was particularly intense. Prominent staining of PDGF was shown at sites of anastomotic hyperplasia and in neovasculature. TGF-beta was associated with proliferation or repair in both AV fistulae and ePTFE grafts. ET-1 staining was most intense in the neointima and pseudointima. This study showed histochemical colocalization of markers of oxidative stress with growth factors known to contribute to intimal hyperplasia.

Topics: Adult; Aged; Arteriovenous Anastomosis; Arteriovenous Fistula; Arteriovenous Shunt, Surgical; Biomarkers; Constriction, Pathologic; Endothelin-1; Female; Growth Substances; Humans; Hyperplasia; Iron; Kidney Failure, Chronic; Lipid Peroxidation; Lysine; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Platelet-Derived Growth Factor; Polytetrafluoroethylene; Renal Dialysis; Transforming Growth Factor beta; Tunica Intima; Vascular Patency

Carvedilol and lacidipine have been shown to exert cardioprotective effects in rat models of chronic hypertension. We investigated their effects in an acute model of pressure overload produced by suprarenal aortic constriction, in which enhanced myocardial production of endothelin-1 could play a crucial role. In the absence of drug treatment, after 1 week, aortic banding provoked an increase in carotid pressure associated with left ventricular hypertrophy (29%; P<0.01). These changes were accompanied by increased myocardial expression of preproendothelin-1 (2.5 times; P<0.05) and skeletal alpha-actin (3.6 times; P<0.05), but the expression of cardiac alpha-actin was not modified. Oral administration of carvedilol at a dose of 30 mg. kg(-1). d(-1) to rats with aortic banding normalized carotid pressure and left ventricular weight as well as preproendothelin-1 and skeletal alpha-actin gene expression. Carvedilol at a lower dose (7.5 mg x kg(-1) x d(-1)) and lacidipine 1 mg x kg(-1) x d(-1) had only moderate and nonsignificant effects on carotid pressure but largely prevented left ventricular hypertrophy (P<0.01) and preproendothelin-1 overexpression (P<0.05). Labetalol (60 mg x kg(-1) x d(-1)) tended to exert similar effects but insignificantly. These results show that the antihypertrophic properties of carvedilol and lacidipine are partly independent of their antihypertensive effects and may be related to their ability to blunt myocardial preproendothelin-1 overexpression. Moreover, carvedilol at a dose of 7.5 mg x kg(-1) x d(-1) did not prevent myocardial overexpression of skeletal alpha-actin, which suggests that, in this model, reexpression of a fetal gene can be activated by pressure overload independently of cardiac hypertrophy.

Topics: Actins; Animals; Antihypertensive Agents; Aortic Diseases; Blood Pressure; Carbazoles; Carotid Arteries; Carvedilol; Constriction, Pathologic; Dihydropyridines; Disease Models, Animal; Endothelin-1; Endothelins; Gene Expression; Heart Rate; Heart Ventricles; Hypertrophy, Left Ventricular; Labetalol; Ligation; Male; Myocardium; Organ Size; Propanolamines; Protein Precursors; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger

Topics: Animals; Bradykinin; Cold Temperature; Constriction, Pathologic; Dilatation, Pathologic; Dinoprost; Endothelin-1; Endothelin-3; Male; Middle Cerebral Artery; Nitroprusside; Parietal Lobe; Rats

Topics: Aged; Aged, 80 and over; Constriction, Pathologic; Endothelin-1; Female; Humans; Postoperative Complications; RNA, Messenger; Saphenous Vein

Endothelin peptides are potent vasoconstrictors and thus are seen as potential cause of cerebral vasospasm after subarachnoid hemorrhage (SAH). Earlier reports showed elevated or normal endothelin levels in plasma and cerebrospinal fluid in patients suffering from SAH. The present study was designed to determine whether endothelin is a causal factor in SAH.. We studied 11 patients with acute SAH. Seven of these 11 patients had a proven aneurysm and six had experienced vasospasm. Big endothelin levels were determined by a radioimmunoassay recognizing the C-terminal peptide (normal range, 1-11 fmol/ml).. There were no elevations of big endothelin in the 59 plasma samples and the 17 simultaneously estimated cerebrospinal fluid samples. Differences between plasma and cerebrospinal fluid did not reach significant levels. Big endothelin values between patients with and without vasospasm showed no significant differences.. Our findings suggest that plasma elevation of the endothelins is not reproducible in SAH and that big endothelin is unlikely to be a causal plasma factor in the complex multifactorial development of vasospasm after SAH.

Topics: Adult; Aged; Aneurysm; Cerebral Arteries; Constriction, Pathologic; Endothelin-1; Endothelins; Female; Humans; Male; Middle Aged; Protein Precursors; Subarachnoid Hemorrhage