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)

We have previously reported that captopril stimulates thromboxane A2 synthesis in patients with essential hypertension. In the present study, the hypotensive effects of captopril and OKY-046, a selective inhibitor of thromboxane A2 synthetase, were studied in nine patients with essential hypertension to determine whether thromboxane A2 is involved in the regulation of blood pressure. A single oral dose of OKY-046 (400 mg) decreased urinary thromboxane B2 (a stable metabolite of thromboxane A2) excretion significantly (from 113 +/- 19.0 to 51.0 +/- 6.1 pg/min; p less than 0.01) and increased urinary sodium excretion significantly (from 73.0 +/- 15.3 to 113.0 +/- 14.4 microEq/min; p less than 0.01), but no change was observed in mean arterial pressure. The administration of OKY-046 (600 mg/day) for 3 days induced a significant and sustained decrease in urinary thromboxane B2 excretion, but it did not affect the mean arterial pressure. Although captopril (50 mg) alone induced a significant increase in urinary thromboxane B2 excretion (from 91.4 +/- 11.0 to 297.3 +/- 30.8 pg/min; p less than 0.001) and a significant decrease in mean arterial pressure (from 97.0 +/- 4.7 to 88.1 +/- 5.1 mm Hg; p less than 0.01), captopril in combination with OKY-046 induced a decrease both in urinary thromboxane B2 excretion (from 70.8 +/- 12.3 to 54.2 +/- 14.7 pg/min; p less than 0.01) and in mean arterial pressure (from 105.1 +/- 3.8 to 84.2 +/- 3.6 mm Hg; p less than 0.01). Thus, the hypotensive effect of captopril was potentiated by OKY-046. OKY-046 did not affect the changes in plasma renin activity and plasma aldosterone concentration and blunted urinary prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion in response to captopril. These results indicate that thromboxane A2 counteracts the hypotensive effect of captopril in patients with essential hypertension.
Hypertension 1988 Feb
PMID:Role of thromboxane A2 in the hypotensive effect of captopril in essential hypertension. 327 11

Neonatal group B streptococcal (GBS) sepsis produces pulmonary arterial hypertension and hypoxemia that are preventable by pretreatment with the selective thromboxane A2 synthase inhibitor, dazmegrel. In the present experiment we administered dazmegrel (8 mg/kg) 2 h after the initiation of a 2 1/2 h infusion of 5 X 10(8) GBS/kg/h in ten 2- to 3-wk-old piglets. The multiple inert gas elimination technique was used to measure intrapulmonary shunt and alveolar ventilation to pulmonary perfusion mismatching. Thromboxane B2, the stable metabolite of thromboxane A2, and 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin, were assayed in arterial blood. Pulmonary arterial pressure increased immediately after initiation of the GBS infusion, rising from 12 +/- 2 to 34 +/- 4 torr (p less than 0.02); pulmonary vascular resistance increased by 400% (p less than 0.01). Arterial hypoxemia developed (p less than 0.02) in association with an increase in the low ventilation-perfusion ratio index but without a significant increase in intrapulmonary shunt. Thromboxane B2 levels increased 10-fold. Infusion of the carrier substance for dazmegrel after 2 h of GBS infusion produced no change in any variables. In contrast, infusion of the drug resulted in the return to pre-GBS infusion baseline values for both pulmonary arterial pressure and pulmonary vascular resistance. However, no improvement in arterial pO2 or in the low ventilation-perfusion ratio index occurred. Both pulmonary vascular resistance and pulmonary arterial pressure remained normal for 0.5 h after dazmegrel administration despite continued GBS infusion. Thromboxane B2 levels were decreased 30 min after dazmegrel (p less than 0.02), but remained greater than pre-GBS levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neonatal group B streptococcal sepsis: effects of late treatment with dazmegrel. 328 20

The renal and systemic metabolites (the latter as 2,3-dinor derivatives) of prostacyclin and thromboxane A2 were measured, along with renal prostaglandin E2 and kallikrein, in the urine of 15 patients with pregnancy-induced hypertension, 15 normotensive pregnant women matched for both age and gestational age, and 15 normotensive nonpregnant control women. Urinary excretion of all prostaglandin and thromboxane metabolites studied proved significantly higher in normotensive pregnant women than in controls. Prostaglandin E2, 6-keto-prostaglandin F1 alpha, and 2,3-dinor-6-keto-prostaglandin F1 alpha were significantly lower in pregnancy-induced hypertensive women than in normotensive pregnant women, whereas thromboxane B2 and 2,3-dinor-thromboxane B2 showed no significant differences in the two groups. A significant negative correlation (r = -0.636, p less than 0.01) was found between urinary 2,3-dinor-6-keto-prostaglandin F1 alpha and mean blood pressure in the two groups of pregnant women taken as a whole. These data indicate that, in pregnancy-induced hypertension, there is an imbalance between vasodilator and vasoconstrictor factors, not only in the kidneys, but also at the systemic vascular level. This imbalance, which may in itself produce vasoconstriction, may also potentiate the hypertensive effect of catecholamines and angiotensin II.
Hypertension 1988 Jun
PMID:Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension. 329 Jan 3

Cyclosporine treatment is associated with hypertension and suppression of plasma renin activity, the causes of which are unclear. To determine whether suppressed plasma renin activity is due to extracellular fluid volume expansion, 10 cyclosporine-treated renal transplant recipients were compared with 10 azathioprine-treated renal transplant recipients and seven patients with renal insufficiency. Glomerular filtration rate and effective renal plasma flow were significantly lower in cyclosporine-treated patients than in azathioprine-treated patients. Upright plasma renin activity was suppressed in cyclosporine-treated patients (cyclosporine 2.9 +/- 0.9, azathioprine 4.7 +/- 0.9, renal insufficiency 5.2 +/- 1.9 ng/ml/hour) but could be stimulated by a four-day period of dietary sodium restriction and diuretic administration (cyclosporine 15.8 +/- 4.4 ng/ml/hour). Extracellular fluid volume tended to be higher in cyclosporine-treated patients (cyclosporine 30.7 +/- 2.3, azathioprine 26.7 +/- 2.5, renal insufficiency 25.5 +/- 1.4 percent lean body mass), although the difference between cyclosporine-treated and azathioprine-treated patients did not attain statistical significance. There were no differences in the urinary excretion of prostaglandin E2 or 6-keto prostaglandin F1 alpha between the two groups of renal transplant recipients. It is concluded that suppression of plasma renin activity by cyclosporine is physiologic and may reflect expansion of extracellular fluid volume, which can be reversed by sodium depletion.
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PMID:Suppression of plasma renin activity by cyclosporine. 330 Mar 26

Phospholipase A2 activity and prostaglandin synthesis were studied in the renal cortex and medulla of stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar-Kyoto rats (WKY) aged 10-50 weeks. Enhanced phospholipase A2 activity was found in both the cortical and the medullary microsomes of SHRSP kidneys. Phospholipase A2 activity progressively increased with age in SHRSP, but not in WKY. Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) were the major prostaglandins found in the cortex, and PGE2 was the major prostaglandin found in the medulla. Prostaglandin l2 (PGI2) was synthesized in both the cortex and medulla, but cortical PGI2 synthesis was much lower than medullary synthesis. Enzymatic activity for all prostaglandin syntheses analysed here were higher in SHRSP. There was a greater age-related increase in prostaglandin synthesis in SHRSP kidneys than in WKY kidneys. In addition, the ratios of PGE2/TXB2 and 6-keto-prostaglandin F1 alpha (PGF1 alpha)/thromboxane B2 (TXB2) decreased in SHRSP. This may produce vasoconstriction and increase vascular resistance in SHRSP. These data suggest that increased prostaglandin synthesis and phospholipase A2 activity have an important role in the development and maintenance of hypertension in SHRSP.
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PMID:Renal prostaglandins and phospholipase A2 in spontaneously hypertensive rats. 330 39

1. The rates of secretion into the circulation of prostaglandin E, prostacyclin, and thromboxane A2 were estimated in male alcoholics on the third day of withdrawal and in control subjects by measuring appropriate metabolites in urine. 2. Urinary levels of tetranor-5,11-diketo-7 alpha-hydroxyprostane-1,16-dioic acid (the major urinary metabolite of prostaglandins E1 and E2), of 2,3-dinor-6-keto-prostaglandin F1 alpha (the major urinary metabolite of prostacyclin) and of 6-keto-prostaglandin F1 alpha (the stable hydrolysis product of prostacyclin) were significantly different from the normal subjects in the alcoholic group. In contrast, 2,3-dinor-thromboxane B2 (the major urinary metabolite of thromboxane A2) and thromboxane B2 (the stable hydrolysis product of thromboxane A2) were not significantly different between the groups. 3. These data suggest that the ratio of the vasodilator prostanoids prostaglandin E and prostacyclin and the vasoconstrictor prostanoid thromboxane A2 is lower than in normal subjects, in alcoholics during withdrawal. This may be one causal factor for the higher incidence of hypertension observed in withdrawing alcoholics compared with control subjects.
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PMID:Decreased systemic formation of prostaglandin E and prostacyclin, and unchanged thromboxane formation, in alcoholics during withdrawal as estimated from metabolites in urine. 325 70

To determine whether the increased renal synthesis of thromboxane (Tx)A2 found in genetically hypertensive rats also occurred in rats with a sodium-dependent form of hypertension, the urinary excretion of 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) and of TxB2 was measured by a sensitive and specific radioimmunoassay in hypertension-prone (SBH), -resistant (SBN) and unselected (SB) female rats of the Sabra strains. Rats of the three strains were studied before (9 weeks of age) and after five weeks of deoxycorticosterone (DOCA)-salt treatment. Before treatment, the urinary 6KPGF1 alpha did not differ among the three strains while a higher TxB2 excretion was seen in the SBN rats. After treatment, the urinary excretion of TxB2 increased significantly in SBH and SB but not in SBN rats, while the urinary 6KPGF1 alpha remained unchanged in SBH, increased moderately in SB and markedly in SBN controls. Consequently, DOCA-salt-induced changes in blood pressure and in urinary 6KPGF1 alpha observed in the three strains of rats were inversely related (r = -0.78; P less than 0.001). It is concluded that the high blood pressure developed after DOCA-salt treatment in SBH rats is more likely to depend upon a defect in the renal production of prostacyclin rather than upon an increased synthesis of thromboxane A2.
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PMID:Effects of DOCA-salt treatment on the urinary prostaglandins in Sabra rats. 339 82

Nonacetylated salicylates have not been reported to cause the hemodynamically mediated acute renal failure associated with nonsteroidal anti-inflammatory drug therapy. A 73-year-old woman with a creatinine clearance of 0.33 mL/s (20 mL/min), hypertension, and arteriosclerotic cardiovascular disease developed reversible renal insufficiency when her dose of salsalate was increased to 4.5 g/d (serum salicylate concentration, 2.22 mmol/L [30.7 mg/dL]). Under close observation the patient was re-treated with lower doses of salsalate while renal function and the urinary excretions of prostaglandins were monitored. The excretion of prostaglandin E2 decreased abruptly while the excretion of 6-keto-prostaglandin F1 alpha decreased more gradually as the dose of salsalate was increased. Renal function appeared to decline in parallel with the decrease in 6-keto-prostaglandin F1 alpha and recovered rapidly after discontinuation of salsalate therapy. Nonacetylated salicylates can cause a hemodynamically mediated acute renal failure in patients at risk for this nephropathy.
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PMID:Salsalate exacerbation of chronic renal insufficiency. Relation to inhibition of prostaglandin synthesis. 347 31

Plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolites of two prostanoids with opposing biological effects, TXA2 and prostacyclin, were measured by radioimmunoassay in normal pregnancy (controls) and pregnancy complicated by hypertension (PIH) from 32 to 36 (Period 1; P1) and from 36 to 40 (Period 2; P2) weeks of gestation. The plasma concentration of each compound in the control subjects was 265.6 +/- 58.4 (TXB2), 132.4 +/- 16.5 (6-keto-PGF1 alpha) for P1 (n = 10) and 142.6 +/- 11.8 (TXB2), 68.5 +/- 5.2 (6-keto-PGF1 alpha) for P2 (n = 10) respectively (pg/ml, mean +/- s.e). In the patients with PIH, TXB2 concentrations increased moderately for P1 (419.2 +/- 21.2; n = 7) and significantly (p less than 0.005) for P2 (452.8 +/- 31.0; n = 7) respectively (pg/ml, mean +/- s.e), while the plasma levels of 6-keto-PGF1 alpha revealed a slight to moderate decrease both for P1 (84.5 +/- 4.0; n = 7) and P2 (59.7 +/- 8.1; n = 7) respectively (pg/ml, mean +/- s.e). The physiological balance of TXB2 to 6-keto-PGF1 alpha was significantly greater (p less than 0.005) in the patients with PIH, where the TXB2/6-keto-PGF1 alpha ratio was 5.2 +/- 0.7 for P1 and 9.4 +/- 2.3 for P2 respectively (mean +/- s.e) compared with that of the controls, where it was 2.4 +/- 0.4 for P1 and 2.0 +/- 0.2 for P2 respectively (mean +/- s.e).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma thromboxane and prostacyclin: comparison during normal pregnancy and pregnancy complicated by hypertension. 353 Jul 28

Patients who develop pregnancy-induced hypertension exhibit a lesser increment in prostacyclin biosynthesis than healthy pregnant subjects. Whether this precedes the development of clinical disease and therefore may be important in the pathogenesis of pregnancy-induced hypertension or is a secondary event is unknown. We prospectively determined prostacyclin biosynthesis in pregnant subjects at risk of developing pregnancy-induced hypertension by use of noninvasive approach, measurement of the urinary metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha. Patients were recruited at less than 20 weeks gestation. After delivery, patients were retrospectively allocated by use of preset criteria, to one of four groups: pregnancy-induced hypertension (n = 12), hypertension in labor (n = 22), chronic hypertension (n = 9), and normotension (n = 24). There was a significant increase in prostacyclin biosynthesis in all study groups during gestation. However, patients who developed pregnancy-induced hypertension exhibited a lesser increment and this difference persisted throughout gestation. These results are consistent with a pathophysiologic role for altered prostacyclin biosynthesis in women with pregnancy-induced hypertension. In addition, decreased prostacyclin formation identifies a population at risk of developing pregnancy-induced hypertension. Such information would assist the design of clinical trials of drugs, such as aspirin, that might prevent the development of this disease.
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PMID:Decreased prostacyclin biosynthesis preceding the clinical manifestation of pregnancy-induced hypertension. 355 97


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