Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

-Renal vascular reactivity is influenced by the level of dietary salt intake. Recent in vitro data suggest that afferent arteriolar contractility is modulated by extracellular chloride. In the present study, we assessed the influence of chloride on K+-induced contraction in isolated perfused rabbit afferent arterioles. In 70% of vessels examined, K+-induced contraction was abolished by acute substitution of bath chloride. Consecutive addition of Cl- (30, 60, 80, 100, 110, and 117 mmol/L) restored the sensitivity to K+, and half-maximal response was observed at 82 mmol/L chloride. The calcium channel antagonist diltiazem (10(-6) mol/L) abolished K+-induced contractions. Bicarbonate did not modify the sensitivity to chloride. Norepinephrine (10(-6) mol/L) induced full contraction in depolarized vessels even in the absence of chloride. Iodide and nitrate were substituted for chloride with no inhibitory effect on K+-induced contraction. Approximately 30% of the vessels constricted in response to K+ in the absence of chloride. This response was reversibly blocked by the alpha1-blocker phentolamine (PA) (10(-5) mol/L) and, with PA present, the dependence on chloride was similar to the above series. The results show that K+-induced contraction of smooth muscle cells in the afferent arteriole is highly sensitive to chloride, whereas neurotransmitter release and ensuing contraction is not dependent on chloride. Thus, there are different activation pathways for depolarizing vasoconstrictors and for the sympathetic nervous system in renal afferent arterioles. This could be of physiological relevance for the resetting of afferent arteriolar sensitivity during changes in salt intake.
Hypertension 1998 Dec
PMID:Chloride regulates afferent arteriolar contraction in response to depolarization. 985 75

Euphorbia hirta is locally used in Africa and Australia to treat numerous diseases, including hypertension and edema. The diuretic effect of the E. hirta leaf extracts were assessed in rats using acetazolamide and furosemide as standard diuretic drugs. The water and ethanol extracts (50 and 100 mg/kg) of the plant produced time-dependent increase in urine output. Electrolyte excretion was also significantly affected by the plant extracts. The water extract increased the urine excretion of Na+, K+ and HCO3-. In contrast, the ethanol extract increased the excretion of HCO3- decreased the loss of K+ and had little effect on renal removal of Na+. Acetazolamide, like the water extract, increased urine output and enhanced the excretion of Na+, K+ and HCO3-. The high-ceiling diuretic, furosemide, increased the renal excretion of Na+ and Cl-; but had no effect on K+ and HCO3- loss. This study suggests that the active component(s) in the water extract of E. hirta leaf had similar diuretic spectrum to that of acetazolamide. These results validate the traditional use of E. hirta as a diuretic agent by the Swahilis and Sukumas.
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PMID:Euphorbia hirta leaf extracts increase urine output and electrolytes in rats. 1035 Mar 69

Cicletanine ((+/-)3-(4-chlorophenyl)-1,3-dihydro-7-hydroxy-6-methylfuro-[3,4-c ] pyridine) 3-(4-chlorophenyl)-1,3-dihydro-7-hydroxy-6-methylfuro-[3,4-c] pyridine) is a novel antihypertensive agent that has been shown to possess vasorelaxant, natriuretic, and diuretic properties in preclinical and clinical studies. The mechanism(s) by which cicletanine induces these biological effects has not been definitely established, although it appears to differ from that of other classes of antihypertensive drugs. The salidiuretic activity appears to be the result of an action of the sulfoconjugated metabolite of cicletanine, which inhibits the apical Na+-dependent Cl-/HCO3- anion exchanger in the distal convoluted tubule. The mechanism of the vasodilating effect of cicletanine seems to be complex; it may include stimulation of vascular prostaglandin synthesis, inhibition of the low Km cyclic GMP phosphodiesterases, and blockade of Ca2+ channels either directly or indirectly through a K+-channel opening effect. The drug has also been shown to interact with alpha-adrenergic, vascular histamine, and muscarinic receptors. We have also reviewed the other vascular effects of the drug, such as stimulation of nitric oxide synthesis and inhibition of both myosin light chain kinase and protein kinase C. Cicletanine protects cardiovascular and renal systems against the injuries induced by hypertension, in addition to its lowering of arterial pressure. Similarly to the vasorelaxant action of cicletanine, the various properties of the drug likely contribute to its protective effect against injury in hypertension.
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PMID:Cicletanine: new insights into its pharmacological actions. 1042 10

Compared to the prehistoric diet, the modern human diet contains not only excessive NaCl and deficient K+, but also deficient precursors of HCO3- and sometimes excessive precursors of nonvolatile acid. The mismatch between the modern diet and the still ancient biological machinery of humans subtly but chronically disorders their internal milieu, giving rise to a prolonged state of low-grade potassium deficiency and low-grade metabolic acidosis whose severity increases with age. Supplemental KCI cannot redress this mismatch and correct this state. However, the mismatch is redressed and the state corrected by restoring intakes of K+ and HCO3- to levels approaching those in the diet of our prehistoric forebearers, with either fruits and vegetables or with supplemental KHCO3. So restored, KHCO3 can: 1) attenuate hypertension and possibly prevent its occurrence by suppressing the phenomenon of normotensive NaCl-sensitivity, in part by its natriuretic effect; (2) prevent kidney stones by reducing urinary excretion of calcium and increasing urinary excretion of citrate; (3) ameliorate and protect against the occurrence of osteoporosis by increasing the renal retention of calcium and phosphorus, and by suppressing bone resorption and enhancing bone formation; and (4) likely prevent stroke.
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PMID:Differing effects of supplemental KCl and KHCO3: pathophysiological and clinical implications. 1051 88

Despite the bioincompatibility of the "old", standard, high glucose, lactate-buffered peritoneal dialysis (PD) solutions, PD is itself a highly successful dialysis modality with patient survival equivalent to that of hemodialysis (HD) during the initial 3 - 5 years of dialysis therapy. Nevertheless, PD technique survival is often limited by infectious complications and alterations in the structure and function of the peritoneal membrane. These local changes also have a negative impact on patient survival owing to systemic effects such as those often seen in patients with high peritoneal transport rate and loss of ultrafiltration (UF) capacity. Patient mortality remains unacceptably high in both HD and PD patients, with most premature deaths being associated with signs of malnutrition, inflammation, and atherosclerotic cardiovascular disease (MIA syndrome). These systemic signs are likely to be influenced by PD solutions both directly and indirectly (via changes in the peritoneal membrane). New, biocompatible PD solutions may have favorable local effects (viability and function of the peritoneal membrane) and systemic effects (for example, on MIA syndrome). Amino acid-based solution [Nutrineal (N): Baxter Healthcare Corporation, Deerfield, IL, U.S.A.] may improve nutritional status as well as peritoneal membrane viability. Bicarbonate/lactate-buffered solution [Physioneal (P): Baxter Healthcare Corporation] may ameliorate local and systemic effects of low pH, high lactate, and high glucose degradation products. Icodextrin-based solution [Extraneal (E): Baxter Healthcare SA, Castlebar, Ireland] may improve hypertension and cardiovascular problems associated with fluid overload and may extend time on therapy in patients with loss of UF capacity. The positive effects of each of these new, biocompatible solutions have been demonstrated in several studies. It is likely that the combined use of N, P, and E solutions will produce favorable synergies in regard to both local effects (peritoneal viability) and systemic effects (less malnutrition, inflammation, and fluid overload). Solution combination is an exciting area for clinical study in the coming years. Furthermore, dialysis fluid additives such as hyaluronan, which protects and improves the function of the peritoneal membrane, may further improve PD solutions. The new, biocompatible PD solutions represent an entirely new era in the evolution of the PD therapy; they are likely to have markedly positive effects on both PD technique and PD patient survival in coming years.
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PMID:Biocompatibility of new peritoneal dialysis solutions: what can we hope to achieve? 1122 14

A prospective study was made on 1068 pupils, aged between 10-15 years (group I). From this group 995 pupils were examined after four to seven years (group II). Their age was between 16-19 years. The study contained: anthropometric data, blood pressure (BP) and pulse measurements, and a standard record using the epidemiologic interview method. For each pupil we determined the following familial and personal antecedent of cardiovascular disease, especially arterial hypertension; alimentary habits (salt and hydro-carbonate excess); consumption of coffee and cigarettes; physical activity; tendency to sedentarism; school or family stress; and behaviour type. Data were worked out and interpreted, using epidemiologic and statistic methods in Epi Info 6 program. The prevalence of genetic factors (4% in group I and 4.3% in group II), consumption of salt (38% in group I and 35% in group II), obesity (1.5% in group and 1.4% in group II), sedentariness (4.8% in group I and 6.8% in group II), stress (9.8% in group I and 10.5% in group II), with behaviour type A (41% I group and 52% in group II) all presented almost equal values in the two groups regardless of age or BP level. The statistical study of the influence of the risk factors on BP values, using student's t test has demonstrated the contributory part of the genetic factor, the excess of sweets and stress. The deleterious effects of arterial hypertension risk factors, which can begin early in childhood demonstrate the necessity for responsible parties (family, school, doctors, etc.) to be aware of these risk factors and assist in their control.
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PMID:[Risk factors in child and adolescent with systemic hypertension]. 1208 30

Although angiotensin (Ang) II is known to regulate renal proximal transport in a biphasic way, the receptor subtype(s) mediating these Ang II effects remained to be established. To clarify this issue, we compared the effects of Ang II in wild-type mice (WT) and Ang II type 1A receptor-deficient mice (AT(1A) KO). The Na+-HCO3- cotransporter (NBC) activity, analyzed in isolated nonperfused tubules with a fluorescent probe, was stimulated by 10(-10) mol/L Ang II but was inhibited by 10(-6) mol/L Ang II in WT. Although valsartan (AT1 antagonist) blocked both stimulation and inhibition by Ang II, PD 123,319 (AT2 antagonist) did not modify these effects of Ang II. In AT1A KO, in contrast, this biphasic regulation was lost, and only stimulation of NBC activity by 10(-6) mol/L Ang II was observed. This stimulation was blocked by valsartan but not by PD 123,319. More than 10(-8) mol/L Ang II induced a transient increase in cell Ca2+ concentrations in WT, which was again blocked by valsartan but not by PD 123,319. However, up to 10(-5) mol/L Ang II did not increase cell Ca2+ concentrations in AT1A KO. Finally, the addition of arachidonic acid inhibited the NBC activity similarly in WT and AT(1A) KO, suggesting that the inhibitory pathway involving P-450 metabolites is preserved in AT(1A) KO. These results indicate that AT(1A) mediates the biphasic regulation of NBC. Although low-level expression of AT(1B) could be responsible for the stimulation by 10(-6) mol/L Ang II in AT1A KO, no evidence was obtained for AT2 involvement.
Hypertension 2002 Nov
PMID:Biphasic regulation of Na+-HCO3- cotransporter by angiotensin II type 1A receptor. 1241 66

Pendrin is an anion exchanger expressed along the apical plasma membrane and apical cytoplasmic vesicles of type B and of non-A, non-B intercalated cells of the distal convoluted tubule, connecting tubule, and cortical collecting duct. Thus, Pds (Slc26a4) is a candidate gene for the putative apical anion-exchange process of the type B intercalated cell. Because apical anion exchange-mediated transport is upregulated with deoxycorticosterone pivalate (DOCP), we tested whether Pds mRNA and protein expression in mouse kidney were upregulated after administration of this aldosterone analogue by using quantitative real-time polymerase chain reaction as well as light and electron microscopic immunolocalization. In kidneys from DOCP-treated mice, Pds mRNA increased 60%, whereas pendrin protein expression in the apical plasma membrane increased 2-fold in non-A, non-B intercalated cells and increased 6-fold in type B cells. Because pendrin transports HCO3- and Cl-, we tested whether DOCP treatment unmasks abnormalities in acid-base or NaCl balance in Pds (-/-) mice. In the absence of DOCP, arterial pH, systolic blood pressure, and body weight were similar in Pds (+/+) and Pds (-/-) mice. After DOCP treatment, weight gain and hypertension were observed in Pds (+/+) but not in Pds (-/-) mice. Moreover, after DOCP administration, metabolic alkalosis was more severe in Pds (-/-) than Pds (+/+) mice. We conclude that pendrin is upregulated with aldosterone analogues and is critical in the pathogenesis of mineralocorticoid-induced hypertension and metabolic alkalosis.
Hypertension 2003 Sep
PMID:Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: role of pendrin in mineralocorticoid-induced hypertension. 1292 56

Several reports have been published in the literature of choreoathetosis associated with lithium intoxication, but little is known about choreoathetosis without concurrent antipsychotic treatment. We report a 65-year-old woman with lithium intoxication whose choreoathetosis completely recovered without sequela following decrease of her serum lithium level. She had been treated elsewhere for bipolar II disorder and also for hypertension, chronic hepatitis type C and diabetes mellitus. As she became hypomanic, lithium carbonate at 600 mg/day was commenced, which was increased to 1200 mg/day due to unfavorable therapeutic response. She began to manifest disorientation and abnormal involuntary movement and was therefore referred to our Department of Psychiatry. Her clinical symptoms at admission included consciousness disturbance with marked bilateral symmetrical slow-wave activity in her EEG and choreoathetosis was observed in her face and upper and lower extremities. Cerebellar symptoms were minimal with only mild ataxic gait and finger-to-nose test did not show dysmetria or intention tremor. Her serum lithium level was 3.52 mEq/L, which was clearly in the toxic range. She demonstrated no metabolic abnormalities including hyperglycemia, and was diagnosed with lithium intoxication and treated with water loading and mannitol for forced diuresis. On the 14th day after admission her consciousness disturbance and choreoathetosis resolved, but EEG abnormalities still persisted. On the 23rd day after admission, she was discharged with clinical remission and normal EEG background activity. Although she developed mild renal dysfunction, hemodialysis was not indicated. Hypersensitivity of dopamine receptor in the nigrostriatal pathways may contribute to choreoathetosis in association with the patient's vulnerability. Choreoathetosis can be a sign of lithium intoxication and prompt treatment is required following careful differential diagnosis.
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PMID:[Reversible choreoathetosis associated with lithium intoxication]. 1463 44

There are many cases of acute subdural hematoma (ASDH) in which acute brain swelling (ABS) occurs intra- or post-operative period and the control of intracranial pressure becomes impossible, resulting in death. Consequently, we investigated the risk factors for ABS in ASDH. Thirteen cases were used for this study. The average age was 53.8 years, and all the subjects were males whose Glasgow Coma Scale (GCS) was an average of 4.8 when hospitalized. We examined the relationship of blood gas values (pH, PaO2, PaCO2, HCO3-, and base excess) when hospitalized, mean arterial blood pressure (MAP) before surgery, and the presence of hypotension during the surgery with ABS. There were no cases, which showed evidence of hypoxia or hypotension when hospitalized or before the surgery. No statistical differences in blood gas values when hospitalized were observed between the 7 cases with ABS and the 6 cases without ABS. However, all of 7 cases with ABS showed MAP > or = 140 mmHg, and 6 cases demonstrated intraoperative hypotension (systolic pressure < 90 mmHg). Conspicuous hypertension before the surgery was shown to be a possible risk factor for ABS. Therefore; MAP > or = 140 mmHg may be a warning sign for the occurrence of ABS.
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PMID:The risk factors for the occurrence of acute brain swelling in acute subdural hematoma. 1475 67


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