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

Coronary heart diseases (CHD) have high indices of mortality and morbidity. A number of CHD and myocardial ischaemic syndromes such as unstable angina pectoris, sudden death ischaemic heart disease, acute myocardial infarction and ventricular arrhythmias have been associated with losses of myocardial magnesium and potassium. Mg++ ions are essential for regulation of Na+ and K+ transport across cell membranes, including those found in cardiac and vascular smooth muscle cells. Mg++ activates an Na+-K+-ATPase pump which in turn plays a major role in regulating Na+-K+ transport. Loss of cellular Mg++ results in loss of critically important phosphagens: MgATP and creatine phosphate. Thus, under conditions where cellular Mg++ is depleted (e.g. hypoxia, ischaemia, anoxia), the Na+-K+ pump and phosphagen stores will be compromised, leading to alterations in resting membrane potentials. Cellular Mg++ depletion has been found to result in concomitant depletion of K+ in a number of cells, including cardiac and vascular muscles. The consequences of these events are often production of cardiac arrhythmias. Myocardial and vascular injury lead to disturbances in electrolyte transport across cell membranes, whereby Na+ and Ca++ uptakes are enhanced and, just prior or concomitantly, Mg++ and K+ are lost. Such electrolyte disturbances often lead to necrotic foci. Considerable evidence has accumulated to indicate that the extracellular concentration of Mg++ is important in control of arterial tone and blood pressure via pressure via regulation of vascular membrane Mg++-Ca++ exchange sites. A reduction in the extracellular Mg++ concentration can produce hypertension, coronary vasospasm and potentiation of vasoconstrictor agents by allowing excess entry of Ca++; concomitantly, the potency of vasodilator agents is reduced. Alterations in vascular membrane Mg++ results in arterial and arteriolar membranes which are 'leaky', thus contributing to the cellular reduction in K+ and gain of Na+ and Ca+. Alterations in extracellular K+ or Na+ concentrations over physiological ranges, in the face of a Mg++ deficit, can exacerbate the coronary vasospasm noted with reduction in only extracellular Mg++. Since free Mg++ ions are necessary for maintaining Ca+ ions (both plasma membrane-bound and sarcoplasmic reticulum membrane-bound via Ca++ ATPases), intracellular free Mg++ would rise in conditions which result in cellular loss of Mg++, thereby exacerbating and contributing to elevation of blood pressure and coronary vasospasm.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Magnesium, electrolyte transport and coronary vascular tone. 614 22

Biochemical and histochemical studies have identified components of the kallikrein-kinin system in the brain. The present study was designed to determine whether kinins could be detected in cerebrospinal fluid (CSF) and if these levels could be altered. Endogenous CSF samples were taken from the cisterna magna of pentobarbital-anesthetized mongrel dogs (n = 11) and were shown to contain 13 +/- 3 pg/ml (mean +/- SE) of immunoreactive kinin ( ikinin ) measured by RIA. The ( ikinin ) samples showed complete parallelism to standard synthetic bradykinin. Ventriculocisternal perfusion of the anesthetized dog brain with artificial CSF alone at a rate of 0.191 ml/min for 240 minutes had little or no effect on basal levels of CSF ( ikinin ), mean arterial pressure (MAP), or heart rate (HR). Melittin (20 microM), an activator of membrane-bound kallikrein, added to the perfusion system for 60 minutes caused a significant and sustained elevation in CSF ( ikinin ) levels from 19 pg/ml up to a maximum of 194 pg/ml (p less than 0.01). This change was accompanied by a prolonged increase in MAP of up to 22 mm Hg (p less than 0.01) and a transient increase in HR of 14 bpm (p less than 0.05). Melittin (2 microM) had no significant effect on CSF ( ikinin ) levels or MAP, but resulted in a sustained increase in HR of 17 to 25 bpm (p less than 0.01). The cardiovascular responses to centrally administered melittin (20 microM) were attenuated by concomitant administration of aprotinin (2000 KIU/ml). This study establishes the existence of ( ikinin ) in the CSF, shows that such levels can be manipulated, and suggests that central kinins may be involved in the modulation of cardiovascular function.
Hypertension
PMID:Cerebrospinal fluid kinins and cardiovascular function. Effects of cerebroventricular melittin. 620 36

Basolateral membrane (BLM) enriched fraction was isolated from homogenized rat kidney cortex by differential centrifugation. We also obtained a fraction enriched in plasma membrane (PM). The morphology of the isolated BLM fragments was studied by transmission and freeze fracture electron microscopy. The relative specific activity of Na+-K+-ATPase was enriched 7-fold, while that of marker enzymes for PM, endoplasmic reticulum, and lysosomes was lower than in the crude homogenate. There was a 10-fold difference in the ratios of activities of Na+-k+-ATPase to Mg2+-ATPase in the BLM and in the PM enriched fractions. Kallikrein activity was determined with S-2266 substrate and by radioimmunoassay of kinin released. It was low in the BLM fraction prior to adding detergent, but Triton X-100 increased the activity 12 to 16-fold. Both free trypsin and Sepharose 4B-bound insoluble trypsin increased kallikrein activity 2- to 3-fold in both the membrane-bound and soluble fractions, probably by activating a prekallikrein. The results were interpreted that the kallikrein studied originated from the distal tubular BLM.
Hypertension
PMID:Kallikrein and prekallikrein on the basolateral membrane of rat kidney tubules. 627 73

1. In 1988, Yanagisawa et al. reported the presence of a potent peptide from the supernatant of porcine endothelial cells. This was later named endothelin-1 (ET-1) and was found to belong to a new family of vasoconstrictor peptides. There are at least three isoforms of endothelin: ET-1, endothelin-2 and endothelin-3. 2. ET-1 is produced from a larger precursor molecule by endothelin converting enzyme (ECE); there may be a number of ECE but the most physiologically relevant appears to be a membrane-bound neutral metalloprotease. The endothelin precursor is produced on demand and is regulated at the mRNA level. 3. Two subtypes of mammalian endothelin receptors have been cloned and sequenced: ETA receptors which mediate vasoconstriction and ETB receptors which mediate both vasoconstriction and vasodilatation. However, functional studies have indicated that other subtypes of endothelin receptors may exist. 4. ET-1 has a wide range of biological actions apart from its direct effects on vascular tone, including constriction of non-vascular smooth muscle, cardiac effects, mitogenesis and stimulation of the release of hormones such as atrial natriuretic peptide and prostacyclin. At low concentrations which have no direct vasoconstrictor action, ET-1 potentiates the effect of other vasoconstrictor agonists. 5. The precise role of ET-1 in health and disease is not well defined at present; however, there are indications that it may have a role in the pathogenesis of some cardiovascular disease states, including subarachnoid haemorrhage, renal ischaemia and certain types of hypertension.
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PMID:Endothelin-1 and the regulation of vascular tone. 755 21

Angiotensin I-converting enzyme (ACE) converts the largely inactive decapeptide angiotensin I to the active octapeptide angiotensin II. ACE is a key component of the renin-angiotensin system that has long been suspected to play a role in the pathogenesis of hypertension and cardiovascular disease. The ACE gene spans 21 kilobases and consists of 26 exons, and two different mRNAs and endothelial and testicular ACE are transcribed from the ACE gene. Circulating ACE probably originates from proteolytic cleavage of the hydrophobic anchor and passive leakage of the membrane-bound enzyme. Normal serum ACE by spectrophotometric assay is very low (8.3-21.4 microliters/ml). The abnormally elevated ACE levels is indeed a diagnostic aid in sarcoidosis. The ACE gene has 287 base pair insertion/deletion polymorphism in intron 16. The ACE deletion polymorphism appears to be associated with increased risk for myocardial infarction in the Caucasian and Japanese population. Recently in multicenter clinical trials (SAVE), administration of inhibitors of ACE were shown to decrease cardiac events after myocardial infarction.
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PMID:[Angiotensin-I converting enzyme]. 760 84

Nitric oxide stimulates endogenous ADP-ribosylation of cytosolic and membrane-bound proteins. Endogenous ADP-ribosyltransferases modify several intracellular proteins including the heterotrimeric GTP-binding proteins (G proteins). ADP-ribosylation of G proteins in vascular smooth muscle leads to increased activation of adenylate cyclase and decreased activation of phospholipase C leading to vasodilation. We hypothesize that in hypertension, chronically depressed endothelium-derived nitric oxide levels lead to decreased ADP-ribosylation of G proteins. This reduced ADP-ribosylation leads to vasoconstriction since activation of the G proteins by agonists is unopposed. Thus, disinhibition of G proteins, mediated by nitric oxide deficit, is responsible for the observed increased sensitivity to vasoconstrictor agonists in hypertension. This novel role for nitric oxide in hypertension will provide a new area of research for antihypertensive therapeutic intervention.
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PMID:Nitric oxide regulation of ADP-ribosylation of G proteins in hypertension. 760 67

Neutral endopeptidase 24.11, a membrane-bound metallopeptidase, cleaves, and degrades vasoactive peptides such as atrial natriuretic peptide, endothelin, angiotensin I, substance P, and bradykinin. Therefore, the presence of this metallopeptidase may contribute to the regulation of vascular tone and local inflammatory responses in the vascular endothelium and elsewhere. We determined neutral endopeptidase in cultured human endothelial cells from different vascular beds and studied its regulation by protein kinase C. Neutral endopeptidase was detected in all cultured endothelial cell types. Lowest concentrations were measured in human endothelial cells from umbilical veins (360 +/- 14 pg/mg protein), followed by pulmonary and coronary arteries; higher concentrations were found in endothelial cells from the cardiac microcirculation (1099 +/- 73 pg/mg protein). Neutral endopeptidase content increased during cell growth but was not affected by endothelial cell growth factor or modifications of the growth medium. Stimulation of protein kinase C with 1-oleoyl-2-acetyl-rac-glycerol (0.1 to 1 mumol/L) and phorbol 12-myristate 13-acetate (0.01 to 0.1 mumol/L) induced a time- and concentration-dependent increase of endothelial cells that was inhibited by cycloheximide (5 mumol/L), an inhibitor of protein synthesis. Incubation with phospholipase C (1 mumol/L) and thrombin (10 IU/mL) induced upregulation of neutral endopeptidase, resulting in 158 +/- 26% and 150 +/- 22% increases, respectively, compared with controls. The thrombin effect was inhibited by calphostin C (1 mumol/L), an inhibitor of protein kinase C. Endothelial neutral endopeptidase is constitutively expressed in endothelial cells from different origins and is inducible by thrombin via activation of the protein kinase C pathway.
Hypertension 1995 Aug
PMID:Regulation and differential expression of neutral endopeptidase 24.11 in human endothelial cells. 763 30

Angiotensin I-converting enzyme (ACE) is known to be present at the surface of endothelial cells and also in the adventitia in large vessels. The presence of ACE in the vascular smooth muscle remains controversial. We microdissected segments of adventitia and media with or without endothelium from a region devoid of collateral arteries. The membrane-bound ACE activity in the media averaged 41% (pmol [glycine-1-14C]hippuryl-L-histidyl-L-leucine hydrolyzed.g tissue-1.min-1) of the values found in the whole aorta, whereas the adventitia contained only 6%. Immunoreactive ACE in media was characterized by Western blotting. ACE mRNAs were detected and characterized after polymerase chain amplification in isolated media. Angiotensin I and angiotensin II were equally able to contract medial rings, and the response to angiotensin I was blocked by enalaprilat. In aortas of two-kidney, one-clip hypertensive rats, there was an increase in ACE mRNA estimated by ribonuclease protection assay (P = 0.02) and in ACE activity at 15 days and 1 and 3 mo after clipping. This corresponded to a 1.5- to 2-fold increase in the ACE activity of both the media and the adventitia compared with sham-operated rats (P < or = 0.02). Thus ACE gene expression occurs in smooth muscle of rat aorta, which contains roughly the same amount of enzyme as the endothelium and readily converts angiotensin I to angiotensin II. ACE in the medial layer and the adventitia is upregulated in renovascular hypertension.
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PMID:ACE in three tunicae of rat aorta: expression in smooth muscle and effect of renovascular hypertension. 797 8

The angiotensin I-converting enzyme (ACE) gene is found on the locus that has been linked to high blood pressure after sodium loading in rats, so in the present study we investigated the role of vascular ACE for the pathophysiology of hypertension in the corresponding parental strains, Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP), in basal conditions at different ages and after sodium loading. Blood pressure was already significantly enhanced in SHRSP from 4 weeks of age, and sodium loading induced an additional increase only in the hypertensive strain. In the aorta, basal ACE gene expression, analyzed by quantitative polymerase chain reaction, and ACE activity were similar in both strains, whereas mRNA levels were elevated in SHRSP after salt compared with WKY rats and correlated with an increase in enzymatic activity. In mesenteric arteries, ACE mRNA levels were significantly enhanced in SHRSP at all ages, although ACE activity was not different between the strains. These results were not modified after sodium loading. These data demonstrate that the level of ACE activity in plasma and vascular tissue can be controlled in a different manner within a rat strain and that in contrast to the soluble form, the membrane-bound ACE may be the one responsible for determining the vasoactive effects of angiotensin II. In addition, ACE undergoes a different regulation in vascular tissues of SHRSP compared with WKY rats, which might be involved in the regulation of blood pressure in these animals.
Hypertension 1994 Sep
PMID:Differential regulation of vascular angiotensin I-converting enzyme in hypertension. 808 33

Coronary heart disease (CHD) is still relatively uncommon in the black population of South Africa. We embarked on a study to determine the prevalence of risk factors leading to CHD in the black population of Durban. The study sample was selected from patients attending a dental clinic at a hospital. A total of 458 Zulus (age range 16-69 years) were studied. The prevalence of CHD was 2.4%. The prevalence percentage of selected risk factors were: hypertension (SBP > or = 140 mmHg and/or a DBP > or = 90 mmHg) was 28%, males 31.9%, females 25.4%; protective levels of high density lipoprotein cholesterol/total cholesterol (HDLC/TC) (> or = 20%) were 81.3%; diabetes, males 4.9%, females 2.9%; smoking > or = ten cigarettes per day, males 28.1%, females 3.4%; obesity, males 3.7%, females 22.6%. We have found the Minnesota Coding System for ECG changes of CHD and Rose questionnaire to be unreliable for eliciting CHD in Blacks. Hypercholesterolaemia is less common and this may explain the low incidence of CHD in Blacks. Epidemics of CHD as seen in the Indian, 'mixed' and white South Africans can still be prevented in the black population but preventive measures must be instituted rapidly.
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PMID:Study of risk factors leading to coronary heart disease in urban Zulus. 811 40


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