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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cocaine is often used while consuming ethanol despite evidence that this combination may enhance the toxicity of cocaine. In the present study, we examined the cardiovascular effects of ethanol (475 or 950 mg/kg, i.v.) alone and in combination with cocaine (5 mg/kg, i.v.) in conscious rats. Ethanol or cocaine administration produced a consistent pressor response but highly variable cardiac output and systemic vascular resistance responses. The hemodynamic response patterns in individual rats to either drug were similar and related within rats. After ethanol pretreatment, cocaine produced greater decreases in cardiac output. We have proposed that this pattern of responses may reflect a predisposition in individual rats to cocaine-induced cardiomyopathies and hypertension. Furthermore, these data suggest that ethanol administration elicits a similar pattern of hemodynamic responses as previously reported for cocaine or amphetamine administration or acute behavioral stress.
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PMID:Ethanol alters hemodynamic responses to cocaine in rats. 933 Sep 17

This study was designed to determine if gender influences the effects of chronic ethanol intake on vasoconstrictive responsiveness. Ethanol-preferring rats were allowed ad libitum access to tap water or tap water containing 20% or 30% ethanol for 16 weeks. All of the ethanol groups consumed more daily calories than their respective controls, and female rats consumed more ethanol calories per unit body mass than their male counterparts. Following treatment, endothelium-intact and endothelium-denuded thoracic aortic rings were used to examine the contractile response to phenylephrine. Ethanol consumption did not alter vasoconstriction in endothelium-intact aortae from either gender. In contrast, males, but not females, demonstrated an ethanol-associated increase in the maximum response to phenylephrine in endothelium-denuded preparations. Aortae from male rats that consumed 20% and 30% ethanol showed an increased contractility of 37% and 85%, respectively. These data indicate that gender influences the vasoconstrictive effects elicited by chronic ethanol consumption and suggest that males may be more susceptible to the associated hypertension.
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PMID:Effects of chronic ethanol consumption on aortic constriction in male and female rats. 1006 52

Ethanol, a risk factor for myocardial dysfunction, depresses myocardial contraction. This study was to determine whether ethanol-induced myocardial depression is affected by hypertension. Mechanical properties of ventricular myocytes isolated from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were evaluated using a video edge-detection system. Myocytes were electrically stimulated to contract at 0.5 Hz. Contractile properties analyzed include peak twitch amplitude (PTA), time-to-PTA (TPS), time-to-90% relengthening (TR(90)), and maximal velocities of shortening/relengthening (+/-dL/dt). Intracellular Ca(2+) transients were measured as fura-2 fluorescence intensity (DeltaFFI) changes. Acute ethanol exposure (80-640 mg/dl) caused a concentration-dependent inhibition of PTA and DeltaFFI in both WKY and SHR myocytes. The extent of maximal inhibition of PTA and FFI was significantly greater in SHRs (53.7 and 38.9%) compared to the WKY group (21.0 and 25.4%). Ethanol did not affect TPS but shortened TR(90) and slowed +/-dL/dt at high concentration ranges. Interestingly, the augmented ethanol-induced inhibition of cell shortening in hypertension was greatly attenuated by Ca(2+) channel opener BayK 8644 (1 microM). These results suggest that ethanol-induced myocardial depression may be augmented in hypertension, possibly due to mechanism(s) involving sarcolemmal Ca(2+) channels.
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PMID:Hypertension augments ethanol-induced depression of cell shortening and intracellular Ca(2+) transients in adult rat ventricular myocytes. 1040 46

The effects of alcohol on blood pressure have been studied extensively. Abstention is recommended in high blood pressure as basic non pharmacological treatment. On the other hand short term lowering of blood pressure by alcohol is known. Blood pressure effects of alcohol vary according to chronicity and amount of intake. It is not known how alcohol affects the 24 hour profile of blood pressure, in particular day- and night-time differences. This explorative study investigates the effects of a single dose of alcohol in the evening on the 24 hour blood pressure profile. Nine individuals with essential hypertension (mean age 65.4 +/- 8.7 years) were compared to 10 normotensives (29.6 +/- 3.0 years). Blood pressure was followed on 2 consecutive days by means of a 24 hour ABPM. On one evening the test persons consumed 0.6 g/kg ethanol before bed time. Apart from the direct comparison of the two groups, effects of body weight and daily alcohol consumption were also considered. For analysis of the 24 hour recording the mean 24 hour values, the mean difference between day and night and loads (fraction of blood pressure > 140/90 mm Hg) as well as heart rate were used. Ethanol led to nocturnal drops of blood pressure in normotensives and hypertensives alike and thus to an increased day/night difference. The latter increased by 2 +/- 4 mm Hg for the systolic and 2 +/- 1 mm Hg for the diastole values in normotensives and by 6 +/- 2 mm Hg and 3 +/- 1 mm Hg, respectively, in hypertensives on the day of alcohol intake. This trend was more marked in individuals with smaller daily alcohol consumption as well as in obese hypertensives. The blood pressure differences were not significant in our test sample because of a large variance in the response. Two normotensives were found to be borderline hypertensives. They exhibited a marked increase of nocturnal blood pressure values above 140/90 mm Hg when compared to the control night. Our study indicates that alcohol consumption should be considered when evaluating 24 hour blood pressure recordings. The blood pressure lowering effect of alcohol during the night is able to modulate the day/night difference can also be useful as diagnostic criterion our data may be clinically relevant.
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PMID:[Effect of alcohol on circadian blood pressure]. 1053 96

Many previous experimental and epidemiological studies have shown that alcohol consumption has a positive correlation with the incidence of hypertension. The effects of ethanol on the nervous and vascular systems in relation to the mechanisms of alcohol-induced hypertension proposed so far are reviewed here. Alcohol ingestion influences many pathophysiological functions which regulate blood pressure, as follows: 1) Sympathetic nervous activity is increased after drinking. 2) Ethanol acts directly on the contractility of vascular smooth muscle. Ethanol acutely contracts some arteries and increases their contractile responses to agonists, while it also displays inhibitory effects on vasocontractility in other arteries. Thus, ethanol has two opposite actions, both of which depend on the kinds of vessels and animal species used for the experiments. Intra- and extracellular Ca2+ mobilization and activation of the contractile apparatus have been suggested as mechanisms for ethanol's vasocontractile actions. 3) Chronic alcohol ingestion has been reported to induce a deficiency of blood and intracellular magnesium, which influences cellular Ca2+ homeostasis through attenuation of plasmalemmal ATPase activity. Direct alcohol effects on cardiovascular systems may not be involved in hypertension that develops after long-term habitual drinking. 4) Ethanol affects vascular endothelial functions, inhibiting endothelial NO- and EDHF-dependent vasorelaxations. 5) The serum levels of vasoactive substances such as cathecolamines, renin-aldosterone, prostacyclin, and endothelin have been reported to be affected by alcohol ingestion or ethanol in vitro. 6) In heavy drinkers, alcohol withdrawal results in an elevation of blood pressure due to sympathetic nervous stimulation. 7) Long-term heavy drinking often results in the development of insulin resistance and glucose intolerance, which in turn triggers hypertension. 8) The difference in the genetic polymorphism of acetaldehyde dehydrogenase among Japanese people may not be directly related to development of alcohol-induced hypertension. As mentioned above, alcohol shows multiple actions on various factors regulating blood pressure. More detailed and integrated mechanisms for alcohol-induced hypertension, which is not a homogeneous disease, remain to be clarified.
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PMID:[Effects of ethanol on the nervous and vascular systems: the mechanisms of alcohol-induced hypertension]. 1126 32

Ethanol has been reported to cause hypertension, the mechanism of which is unknown. Therefore, the effect of chronic ethanol consumption on vascular responsiveness and blood pressure was investigated. Systolic blood pressure was recorded weekly by tail-cuff method. Aortic rings from rats fed chow ad libitum or pair-fed liquid diets containing either ethanol (7.2% v/v) or isocaloric carbohydrate for 4 weeks were placed in organ chambers for isometric tension measurement. There was a mild but significant elevation of the systolic blood pressure in the alcohol-fed rats by week 1 compared to baseline measurements and this remained higher. No significant changes in reactivity of rat isolated aortas to phenylephrine, serotonin, endothelin-1 (ET-1) and KCl were seen in chronic ethanol consumption. In addition, the sensitivity (i.e. pD2) of alcohol-fed aortic rings to the vasoconstrictors was also unchanged compared to controls. Chronic ethanol consumption, however, increased relaxation to acetylcholine with increased pD2 values, but did not alter relaxation to sodium nitroprusside, a cyclic guanosine monophosphate (cGMP)-dependent direct smooth muscle dilator. The results indicate that chronic ethanol consumption significantly potentiates endothelium-dependent relaxations in aortic rings, probably through interference with the production and/or the release of nitric oxide (NO) or adaptive alterations in muscarinic receptors on the endothelial cells, and that increased vascular responsiveness to several vasoconstrictors is not a mechanism responsible for the blood pressure elevation in the chronic alcohol consumption in rats.
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PMID:Blood pressure and vascular reactivity to endothelin-1, phenylephrine, serotonin, KCl and acetylcholine following chronic alcohol consumption in vitro. 1146 26

Ethanol causes vasoconstriction and contributes to the development of hypertension. Acetaldehyde (ACA), the primary metabolite of ethanol, elevates blood pressure by releasing endogenous catecholamines. In vitro, ACA leads to vasorelaxation, although the response may vary among various vascular beds. This study examined the influence of hypertensive state on the ACA-induced vasorelaxant responsiveness. Ring segments of thoracic aorta were isolated from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) and isometric tension development was measured. In aorta with or without intact endothelium, the contractile responses to KCl and norepinephrine were greatly attenuated, whereas vasoconstrictive response to 5-HT was enhanced, by hypertension. Vasorelaxant response to histamine was similar between WKY and SHR groups. ACA (1-30 mM) elicited endothelium-intact as well as -denuded vasorelaxation in a dose-dependent manner in aorta from both WKY and SHR groups. Interestingly, the ACA-induced endothelium-intact vasorelaxation was significantly diminished, whereas the ACA-induced endothelium-denuded vasorelaxation was significantly augmented, by hypertension. These data indicated that the ACA-induced vasorelaxant response, either endothelium-intact or-denuded, is altered by the hypertensive state.
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PMID:Influence of hypertension on acetaldehyde-induced vasorelaxation in rat thoracic aorta. 1188 15

Insights into the relations between and among ethanol-induced contractions in rat aorta, tyrosine kinases (including src family of cytoplasmic tyrosine kinases), 1-phosphatidylinositol 3-kinases (PI-3Ks), mitogen-activated protein kinases (MAPKs), and regulation of intracellular free Ca(2+) ([Ca(2+)](i)) were investigated in the present study. Ethanol-induced concentration-dependent contractions in isolated rat aortic rings were attenuated greatly by pretreatment of the arteries with low concentrations of an antagonist of protein tyrosine kinases (genistein), an src homology domain 2 (SH2) inhibitor peptide, a highly specific antagonist of p38 MAPK (SB-203580), a potent, selective antagonist of two specific MAPK kinases-MEK1/MEK2 (U0126)-and a selective antagonist of mitogen-activated protein kinase kinase (MAPKK) (PD-98059), as well as by treatment with wortmannin or LY-294002 (both are selective antagonists of PI-3Ks). Inhibitory concentration 50 (IC(50)) levels obtained for these seven antagonists were consistent with reported inhibition constant (Ki) values for these tyrosine kinase, MAPK, and MAPKK antagonists. Ethanol-induced transient and sustained increases in [Ca(2+)](i) in primary single smooth muscle cells from rat aorta were markedly attenuated in the presence of genistein, an SH2 domain inhibitor peptide, SB-203580, U0126, PD-98059, wortmannin, and LY-294002. A variety of specific antagonists of known endogenously formed vasoconstrictors did not inhibit or attenuate either the ethanol-induced contractions or the elevations of [Ca(2+)](i). Results of the present study support the suggestion that activation of tyrosine kinases (including the src family of cytoplasmic tyrosine kinases), PI-3Ks, and MAPK seems to play an important role in ethanol-induced contractions and the elevation of [Ca(2+)](i) in smooth muscle cells from rat aorta. These signaling pathways thus may be important in hypertension in human beings associated with chronic alcohol consumption.
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PMID:Roles of tyrosine kinase-, 1-phosphatidylinositol 3-kinase-, and mitogen-activated protein kinase-signaling pathways in ethanol-induced contractions of rat aortic smooth muscle: possible relation to alcohol-induced hypertension. 1237 57

Pediatric renovascular hypertension is an uncommon but important clinical problem. Atherosclerosis is rare in children, who typically suffer from fibromuscular dysplasia, neurofibromatosis type 1, Williams syndrome, or certain other rare conditions. Children with renovascular disease often have involvement of other arteries including the aorta and mesenteric and cerebral vessels. The pediatric interventional radiology service has a vital role in the diagnosis, evaluation, and treatment of renovascular hypertension. Renal vein renin sampling appears to be more useful in children than in adults, because their arterial disease is more often bilateral and segmental. Diagnostic angiography is still superior to less-invasive methods of imaging the renal arteries, especially the smaller branches. Interventional options include angioplasty, stenting, and ethanol ablation. Angioplasty is almost always technically successful and usually gives a worthwhile clinical improvement. Stenting is only used in children when angioplasty fails. Ethanol embolization may be appropriate in children with focal renin-producing areas that are untreatable by angioplasty.
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PMID:Interventional radiology for renovascular hypertension in children. 1476 46

Chronic ethanol abuse is associated with liver injury, neurotoxicity, hypertension, cardiomyopathy, modulation of immune responses and increased risk for cancer, whereas moderate alcohol consumption exerts protective effect on coronary heart disease. However, the signal transduction mechanisms underlying these processes are not well understood. Emerging evidences highlight a central role for mitogen activated protein kinase (MAPK) family in several of these effects of ethanol. MAPK signaling cascade plays an essential role in the initiation of cellular processes such as proliferation, differentiation, development, apoptosis, stress and inflammatory responses. Modulation of MAPK signaling pathway by ethanol is distinctive, depending on the cell type; acute or chronic; normal or transformed cell phenotype and on the type of agonist stimulating the MAPK. Acute exposure to ethanol results in modest activation of p42/44 MAPK in hepatocytes, astrocytes, and vascular smooth muscle cells. Acute ethanol exposure also results in potentiation or prolonged activation of p42/44MAPK in an agonist selective manner. Acute ethanol treatment also inhibits serum stimulated p42/44 MAPK activation and DNA synthesis in vascular smooth muscle cells. Chronic ethanol treatment causes decreased activation of p42/44 MAPK and inhibition of growth factor stimulated p42/44 MAPK activation and these effects of ethanol are correlated to suppression of DNA synthesis, impaired synaptic plasticity and neurotoxicity. In contrast, chronic ethanol treatment causes potentiation of endotoxin stimulated p42/44 MAPK and p38 MAPK signaling in Kupffer cells leading to increased synthesis of tumor necrosis factor. Acute exposure to ethanol activates pro-apoptotic JNK pathway and anti-apoptotic p42/44 MAPK pathway. Apoptosis caused by chronic ethanol treatment may be due to ethanol potentiation of TNF induced activation of p38 MAPK. Ethanol induced activation of MAPK signaling is also involved in collagen expression in stellate cells. Ethanol did not potentiate serum stimulated or Gi-protein dependent activation of p42/44 MAPK in normal hepatocytes but did so in embryonic liver cells and transformed hepatocytes leading to enhanced DNA synthesis. Ethanol has a 'triangular effect' on MAPK that involve direct effects of ethanol, its metabolically derived mediators and oxidative stress. Acetaldehyde, phosphatidylethanol, fatty acid ethyl ester and oxidative stress, mediate some of the effects seen after ethanol alone whereas ethanol modulation of agonist stimulated MAPK signaling appears to be mediated by phosphatidylethanol. Nuclear MAPKs are also affected by ethanol. Ethanol modulation of nuclear p42/44 MAPK occurs by both nuclear translocation of p42/44 MAPK and its activation in the nucleus. Of interest is the observation that ethanol caused selective acetylation of Lys 9 of histone 3 in the hepatocyte nucleus. It is plausible that ethanol modulation of cross talk between phosphorylation and acetylations of histone may regulate chromatin remodeling. Taken together, these recent developments place MAPK in a pivotal position in relation to cellular actions of ethanol. Furthermore, they offer promising insights into the specificity of ethanol effects and pharmacological modulation of MAPK signaling. Such molecular signaling approaches have the potential to provide mechanism-based therapy for the management of deleterious effects of ethanol or for exploiting its beneficial effects.
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PMID:MAP kinase signaling in diverse effects of ethanol. 1502 49


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