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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the hemodynamic effects of continuous i.v. infusion of endothelin-1 and big endothelin-1 in anesthetized rats. Big endothelin-1 was fivefold less potent than endothelin-1 in decreasing cardiac output, heart rate, and stroke volume. However, big endothelin-1 produced a significantly larger increase in mean arterial pressure compared to endothelin-1 at doses that produced identical decreases in cardiac output. These findings support the hypothesis that the hypertensive effects of big endothelin-1 and endothelin-1 are produced by differential effects on systemic vascular resistances.
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PMID:Comparison of the hemodynamic effects of endothelin-1 and big endothelin-1 in the rat. 189 93

1. The tissue-protective effects of calcium channel blockers in hypertension are not well dissociated from their effect on systolic blood pressure (SBP). We have previously shown that lacidipine, a dihydropyridine-type calcium antagonist, reduced the cardiac hypertrophy and the cardiac endothelin-1 (ET-1) gene overexpression occurring in salt-loaded stroke-prone spontaneously hypertensive rats (SL-SHRSP), an effect occurring without systolic blood pressure (SBP) change. In the present study, we have examined whether this action was dose-related and if it could be associated with ET receptor changes. The action of lacidipine was also examined in control SHRSP and in Wistar Kyoto rats (WKY). 2. The daily dose of 0.3 mg kg-1 lacidipine which did not lower SBP but significantly prevented ventricle hypertrophy and cardiac preproET-1-mRNA expression in SL-SHRSP was inactive in control SHRSP. With the higher dose of lacidipine (1 mg kg-1 day-1), we observed a further reduction of cardiac hypertrophy and of ET-1 gene expression in SL-SHRSP and a significant effect on those parameters in control SHRSP but only a small reduction of SBP in both groups. 3. In WKY, salt loading did not induce change in SBP or increase of cardiac ET-1 gene expression and ventricle mass. In these normotensive rats, lacidipine (1 mg kg-1 day-1) did not modulate the basal preproET-1-mRNA expression and did not affect SBP or heart weight. 4. The maximum binding capacity (Bmax) and the dissociation constant (KD) of [125I]-ET-1 binding and the relative proportion of low- and high-affinity binding sites for ET-3 were not significantly affected by salt loading or lacidipine treatment in SHRSP. 5. These results show that lacidipine exerted a dose-related inhibition of ventricle hypertrophy and preproET-1-mRNA expression in SHRSP and indicate that this effect was unrelated to SBP changes. The dose-dependency of this inhibition suggests that salt-induced cardiac hypertrophy could be related to ET-1 gene overexpression. The results further show that ET receptor changes are not involved in the pathophysiological process studied here.
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PMID:Action of the calcium channel blocker lacidipine on cardiac hypertrophy and endothelin-1 gene expression in stroke-prone hypertensive rats. 876 91

Big endothelin-1 (Big ET-1) was given intravenously to six healthy men to study uptakes and vascular effects. Blood samples were taken from systemic and pulmonary arterial and internal jugular and deep forearm venous catheters. Arterial Big ET-1-like immunoreactivity (Big ET-1-LI) increased from 5.43 +/- 0.60 to 756 +/- 27 pmol/l, and ET-1-LI increased from 4.67 +/- 0.08 to 6.67 +/- 0.52 pmol/l (P < 0.001). Skeletal muscle fractional extraction of Big ET-1-LI was 15 +/- 4%. ET-1-LI release did not increase in the studied vascular beds. Heart rate fell by 17% (P < 0.001), cardiac output fell by 26% (P < 0.001), and stroke volume fell by 11% (P < 0.05). Mean arterial blood pressure increased 18%, systemic vascular resistance increased 65%, and pulmonary vascular resistance increased 57% (P < 0.01-0.001). Pulmonary blood pressures, forearm blood flow, arterial pH, arterial PCO2, and systemic arterial-internal jugular venous O2 difference remained unchanged. No specific Big ET-1 receptors were found in human pulmonary membranes. The half-maximal inhibitory concentration for the receptor antagonist bosentan was 181 nM. In summary, circulating Big ET-1 elicits greater increases in mean arterial blood pressure and systemic vascular resistance and decreases in heart rate and cardiac output compared with an equimolar ET-1 infusion (26).
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PMID:Central and regional hemodynamic effects during infusion of Big endothelin-1 in healthy humans. 880 95

The single oral administration of a mixed endothelin-A-and -B- (ETA/ETB) receptor antagonist, J-104132 (L-753,037) decreased the blood pressure in conscious spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and Dahl salt-sensitive hypertensive rats fed high-salt diet (DS-H) at doses of 3 and 10 mg/kg, with a duration of approximately 24 h. The magnitude of the antihypertensive effects was greater in DS-H than in SHR and SHRSP Preproendothelin-1 mRNA expression in the kidney and aorta was greater (about twofold) in DS-H than that in nonnotensive Dahl salt-resistant rats fed high-salt diet (DR-H), while there was no difference in preproendothelin-1 mRNA expression between SHR and Wistar Kyoto rats (WKY). An AT1-receptor antagonist, MK-954 (Losartan), also attenuated hypertension in SHR and SHRSP at oral doses of 3 and 10 mg/kg, but bad no effect in DS-H. The concomitant treatment with MK-954 and J-104132 showed additive antihypertensive effects in SHR and SHRSP. In DS-H, MK-954 potentiated the antihypertensive effects of J-104132. From these results, we suggest that: (1) the contribution of endothelin (ET) to the maintenance of hypertension is greater in salt-sensitive hypertensive models than in SHR and SHRSP; (2) the antihypertensive efficacy of ETA/ETB blockade is augmented by AT1-receptor blockade; (3) ET blockers alone or in combination with AT1 antagonists could be useful in the treatment of hypertension for patients who do not respond adequately to renin-angiotensin system inhibitors alone.
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PMID:Antihypertensive effects of a mixed endothelin-A- and -B-receptor antagonist, J-104132, were augmented in the presence of an AT1 -receptor antagonist, MK-954. 1107 14

An association exists between infection and cardiovascular diseases, including atherosclerosis, stroke and myocardial infarction. This may involve endothelin-1 (ET-1) which has been implicated in these and other vascular pathologies. ET-1 synthesis is controlled primarily by the level of its mRNA and numerous stimuli, including infection, lead to elevated ET-1 levels. Here, we have investigated the regulation of ET-1 release and preproET-1 (ppET-1) mRNA in bovine aortic endothelial cells by lipopolysaccharide (LPS). ET-1 release from bovine aortic endothelial cells was stimulated by LPS and reporter gene assays implicated LPS-induced ppET-1 transcription. However, changes in transcription were modest compared to increases in ET-1 synthesis. Therefore, ppET-1 mRNA levels were measured by real-time reverse transcription-polymerase chain reaction. The effect of LPS on ppET-1 mRNA levels was more marked than on transcription (1.2-fold increase in transcription vs. 5.5-fold increase in ppET-1 mRNA). Analysis of ppET-1 mRNA stability by real-time reverse transcription-polymerase chain reaction showed that LPS increased its half-life by approximately 2-fold. Thus, upregulated ppET-1 mRNA and hence increased ET-1 synthesis may be due to both increased transcription and reduced mRNA degradation. These effects of LPS on mRNA stability may be a key mechanism in vascular pathologies through which many proteins are induced in response to infection.
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PMID:A role for increased mRNA stability in the induction of endothelin-1 synthesis by lipopolysaccharide. 1290 23

Endothelin-1 (ET-1) has been implicated in hypertension, heart failure, atherosclerosis, and pulmonary hypertension. In all these conditions, plasma immunoreactive ET-1 levels are elevated, and tissue ET-1 expression is increased. Clinical trials have demonstrated potentially important benefits of ET antagonism among patients with essential hypertension, pulmonary hypertension, and heart failure. It is unknown whether ET antagonism affects the production of ET-1 in stroke-prone spontaneously hypertensive rat (SHRSP) heart at the typical hypertensive stage. The objective of this study was to investigate the effects of ET blockade on the expression levels of plasma and cardiac ET-1 in SHRSPs. SHRSPs were treated for 3 months with SB209670 (ET(A)/ET(B) dual receptor antagonist) or with saline (vehicle) commencing at the prehypertensive stage (age 6 weeks). Plasma and left ventricular ET-1 peptide levels were measured using enzyme-linked immunoabsorbent assay. Compared with age-matched control Wistar-Kyoto rats, peptide levels of ET-1 were significantly upregulated in vehicle-treated SHRSP heart; this upregulation was reversed by long-term ET antagonism. Plasma ET-1 levels were also significantly increased in vehicle-treated SHRSPs and were normalized by ET antagonism. mRNA expression of preproET-1, which is the source of ET-1 peptide production, was significantly increased in vehicle-treated SHRSP heart and was normalized by ET antagonism. Marked cardiac hypertrophy and fibrosis at the histologic level in SHRSPs were ameliorated by ET antagonism, and left ventricular hypertrophy as seen on echocardiography in SHRSPs was suppressed by ET blockade. After ET antagonism, systolic blood pressures were reduced in SHRSPs; diastolic blood pressures were unchanged. The reversal effect of the upregulated ET system in SHRSP heart by ET antagonism might be independent of blood pressure change. By suppressing the upregulated ET system, ET antagonism might be beneficial in arresting cardiac remodeling.
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PMID:Endothelin antagonism suppresses plasma and cardiac endothelin-1 levels in SHRSPs at the typical hypertensive stage. 1674 Oct 24