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)

Cells were isolated from the outer medulla of the rabbit kidney, primarily from the thick ascending limb of Henle's loop (mTALH). These mTALH cells are heavily invested with a cytochrome P450-linked monooxygenase that represents the third pathway by which arachidonic acid is metabolized. After cell separation, approximately 80% of the cells proved to be mTALH in origin, based on electron microscopic criteria and immunofluorescent localization of Tamm-Horsfall protein, a specific marker for mTALH cells. The specific activity of alkaline phosphatase, a marker for proximal tubular cells, decreased threefold after separation of mTALH cells from outer medullary cells, associated with a fourfold increase in the capacity of the separated mTALH cells to metabolize arachidonic acid. Incubation of mTALH cells with 14C-arachidonic acid resulted in formation of oxygenated metabolites, identified as two peaks (P1 and P2), which accounted for 30 to 40% of the recovered radioactivity. Formation of prostaglandin E2 and F2 alpha accounted for only 3 to 5%. The chromatographic retention times of P1 and P2 were different from products of lipoxygenases. An inhibitor of cytochrome P450-dependent enzymes, SKF-525A (50 microM), reduced product formation by mTALH cells by more than 70%, while induction of cytochrome P450 increased product formation. Formation of P1 and P2 by cell-free homogenates of mTALH was totally dependent on the presence of nicotinamide adenine dinucleotide phosphate, reduced form (NADPH), which suggests a NADPH-dependent cytochrome P450-linked monooxygenase pathway. Vasopressin and calcitonin (10(-10) M to 10(-7) M) stimulated release of arachidonic acid metabolites from mTALH cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Renal arachidonic acid metabolism. The third pathway. 298 23

In a prospective study of 21 normal human kidney donors, increases in blood pressure were found in seven of 12 males and in three of nine females within the first year after uninephrectomy. Donors with blood pressure increases were characterized by greater weight and body mass indexes. In addition, urinary phosphate excretion was positively correlated (r = 0.73, p less than 0.001) and tubular reabsorption of phosphate negatively correlated (r = -0.61, p less than 0.01) with blood pressure at the follow-up periods in which increases were observed. All donors experienced an increase in parathyroid hormone levels and urinary cyclic AMP excretion. These changes were accompanied by decreases in urinary calcium and serum phosphate values. Thus, the increase in blood pressure took place in a milieu similar to that of "normocalcemic" hyperparathyroidism. The correlation of phosphate excretion and blood pressure in normal donors suggests an important role for phosphate metabolism in the genesis of hypertension associated with loss of renal mass.
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PMID:Divalent ion handling in human kidney donors with increased blood pressure after uninephrectomy. 301 74

The production of [3H]-inositol phosphates was studied in labelled segments of aorta from spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls at 5 and 19 weeks, either unstimulated or in the presence of noradrenaline. Basal hydrolysis of inositol phospholipids was significantly enhanced in young SHR (P less than 0.05) compared to controls but this difference was no longer detected at 19 weeks. Noradrenaline increased [3H]-inositol phosphate accumulation in both SHR and WKY, but maximal hydrolysis was significantly greater in WKY (P less than 0.01), although the ED50 was similar in both groups of animals. These data demonstrate that phosphatidylinositide hydrolysis is enhanced in the young hypertensive rat at the time blood pressure is rising, but that this activity has declined by the time hypertension has reached an established phase. In addition, alpha 1-agonist induction of inositol phospholipid hydrolysis differs in the two species of animals, being reduced in genetically mature hypertensive rats.
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PMID:Abnormal vascular phosphoinositide hydrolysis in the spontaneously hypertensive rat. 302 53

Alterations of cellular function of Na+,K+-adenosine triphosphatase (ATPase; Na+-K+ pump) have been implicated in the pathophysiology of essential hypertension. Therefore, this aspect of red blood cell (RBC) Na metabolism was studied in black men with newly diagnosed, untreated essential hypertension (NEH) and a normotensive control group. RBC Na content, Na+-K+ pump number (ouabain binding sites), and pump activity were measured. No statistically significant differences were found between the two groups for any of these three parameters. However, a group of previously treated essential hypertensive subjects (PEH) who had been withdrawn from therapy in the preceding 6 weeks were also studied. This group differed significantly from the NEH subjects in regard to all RBC Na+-K+ pump parameters. Their RBC Na content (10.27 +/- 3.23 vs 7.77 +/- 2.52 mmol Na/LRBC; p = 0.006) was higher, and their Na+-K+ pump activity (166 +/- 50 vs 221 +/- 87 nmol inorganic phosphate/mg membrane protein/hr; p = 0.03) and Na+-K+ pump number (213 +/- 40 vs 284 +/- 85 binding sites/RBC; p = 0.001) were lower compared with those in NEH subjects. Although the PEH subjects were older and somewhat less hypertensive than their NEH counterparts, these factors were not found to influence the Na+-K+ pump parameters. These results indicate that chronic diuretic therapy of patients with essential hypertension is associated with a reduced number of RBC Na+-K+ pumps. Since RBCs are not considered target cells for diuretics, the effects of these drugs on RBC electrolyte metabolism may occur at the time of erythropoiesis by the production of RBCs with fewer Na+-K+ pumps.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1987 May
PMID:Red blood cell Na+,K+-ATPase in men with newly diagnosed or previously treated essential hypertension. 303 88

The metabolism of phosphoinositides was investigated in erythrocyte membranes of essential hypertensive patients, normotensive offspring of hypertensive patients and matched controls. Measurement of 32P-labelling of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate revealed no differences in the rate of incorporation of the isotope in essential hypertensive patients compared with controls. In the normotensive offspring of essential hypertensive patients there was a highly significant increase in the rate of 32P incorporation (P less than 0.01), compared with matched controls, indicating a higher rate of metabolic turnover in these subjects. These data demonstrate that phosphoinositide metabolism is enhanced in subjects genetically at risk of hypertension, before the blood pressure has risen, but once the blood pressure is established, it is no different from control values. Abnormal phosphoinositide metabolism may be a further manifestation of a genetically determined defect of membrane physicochemical function underlying essential hypertension.
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PMID:Erythrocyte phosphoinositide metabolism in essential hypertensive patients and their normotensive offspring. 303 55

To examine the relationship between body mass index, blood pressure, and the Na+,K+-adenosine triphosphatase (ATPase) system, we measured the erythrocyte ghost Na+,K+-ATPase and the erythrocyte Na+ concentration in 120 blacks and 127 whites (136 males and 111 females). Blacks showed a 13.9% higher erythrocyte Na+ (7.63 +/- 0.19 vs 6.70 +/- 0.11 [SEM] mEq/L; p = 0.0001) and a 16.1% lower erythrocyte ghost Na+,K+-ATPase activity (140.3 +/- 4.2 vs 167.3 +/- 4.7 nmol inorganic phosphate/mg protein/hr; p = 0.0002) than whites. Male subjects demonstrated a 6.4% higher erythrocyte Na+ (7.35 +/- 0.17 vs 6.91 +/- 0.14 mEq/L; p = 0.043) and an 11.5% lower Na+,K+-ATPase activity (145.7 +/- 3.7 vs 164.7 +/- 5.5 nmol inorganic phosphate/mg protein/hr; p = 0.0015) than female subjects. Significant (p less than 0.001) negative correlations were identified for the systolic, diastolic, and mean blood pressure levels and the erythrocyte ghost Na+,K+-ATPase. These findings were complemented by positive correlations for the blood pressure levels and erythrocyte Na+ concentrations. The body mass index was negatively correlated with erythrocyte ghost Na+,K+-ATPase and it accounted for 6.7%, 5.6%, and 6.1% of the variabilities in the systolic, diastolic, and mean blood pressure levels, respectively. Variabilities of 1.4% systolic, 12.3% diastolic, and 11.1% in mean arterial pressure were attributable to the erythrocyte ghost Na+,K+-ATPase activity. Provided that findings in erythrocytes also reflect the relative status of the vascular smooth muscle cell Na+,K+-ATPase, the predisposition of black, male, and obese persons to hypertension may relate, among other factors, to a lower activity of this enzyme system, which results in an increased vascular tone.
Hypertension 1987 Sep
PMID:Erythrocyte ghost Na+,K+-ATPase and blood pressure. 304 May 86

Patients with pyelonephritic renal scarring are at risk of developing renal failure and hypertension. We studied glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction (FF), systolic (SBP) and diastolic (DBP) blood pressure, fractional sodium, potassium and phosphate excretion, peripheral renin activity (PRA), plasma aldosterone (p-Aldo), urinary albumin excretion (U-Alb) and urinary beta 2-microglobulin excretion (beta 2-M) in hydropenia and during transition to 3% volume expansion with isotonic saline infusion in 22 female patients with renal scarring due to pyelonephritis and 9 healthy controls. The patients had significantly lower GFR, higher SBP and higher PRA in hydropenia, but there was no significant difference in RPF, FF, DBP or p-Aldo. After volume expansion, SBP, DBP, PRA and p-Aldo were significantly higher in patients than in controls. Transition to 3% volume expansion was associated with a similar increase in SBP in both patients and controls, whereas DBP increased significantly more in the patients (p less than 0.01). Volume expansion resulted in a significant suppression of PRA and p-Aldo in both patients and controls. The patients with renal scarring had the same capacity to excrete sodium and water during transition to volume expansion as the healthy controls. The renin-aldosterone system seems abnormally activated and is probably more important than hypervolemia in the development of hypertension in this group of patients.
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PMID:Role of hypervolemia and renin in the blood pressure control of patients with pyelonephritis renal scarring. 304 33

Treatment of diabetics with end-stage renal failure is still a hazard. We report on 33 insulin-dependent diabetic patients who were treated with CAPD over a period of up to 70 months. Seven of them have been transplanted. The evaluation of the clinical and biological parameters serum protein, phosphate, calcium, revealed acceptable values. Hemoglobin rose during the treatment period. Hypertension improved and medication was reduced. HbAlc levels were near normal with subcutaneous application of insulin. Peritonitis rate was 1/18 patient-months. Survival rate was comparable with other centers with 83% in the first and 62% in the second year. In 7 patients that have been transplanted no CAPD-related problems arose after transplantation. 6 of them are still doing well; one returned to CAPD because of graft failure. In conclusion, because of good control of hypertension, blood glucose and anemia and the avoidance of fluctuating volumes, we think CAPD to be the best method for diabetics awaiting transplantation and for those that cannot be transplanted.
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PMID:CAPD and transplantation in diabetics. 305 57

In uremia, parathormone (PTH) has been associated with inadequate left ventricular hypertrophy, cardiomyopathy, and mitral anular calcification (MAC). We related levels of serum PTH, calcium, phosphate, magnesium, calcium-phosphate product, and systolic blood pressure to average left ventricular wall thickness, left ventricular mass index, ejection fraction, and presence and extent of MAC by echocardiography in 44 patients before and after renal transplantation. Pre-transplant, 18 patients (41%) had MAC; these and the 26 others had similar values for serum PTH, calcium-phosphate product, systolic blood pressure, age, and years of hemodialysis. The patients with PTH levels greater than 1000 mcl eq/ml had higher systolic blood pressures pre-transplant (157 +/- 21 vs 147 +/- 17 mm Hg, p less than 0.05), but not post-transplant as PTH levels normalized. Post-transplant, there were significant decreases in left ventricular mass index (140 +/- 35 to 103 +/- 25 g/m2) and average diastolic left ventricular wall thickness (1.4 +/- 0.2 to 1.2 +/- 0.2 cm, both p less than 0.05); however, ejection fraction and extent of MAC did not change. Left ventricular mass index, average diastolic left ventricular wall thickness, and ejection fraction did not correlate with serum PTH or electrolyte levels before or after renal transplantation. MAC is present in more than one third of uremic pts and does not resolve after renal transplantation. Although PTH does not correlate with left ventricular hypertrophy, cardiac function, or MAC before or after transplantation, elevated levels pre-transplant are associated with a slightly greater degree of hypertension. Thus PTH may be a mild vasoactive pressor in some patients with end-stage renal failure.
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PMID:Is parathormone a cardiac toxin in uremia? 307 28

The impending release of erythropoietin (EPO) is expected to result in a dramatic increase in hematocrit (Hct) for most hemodialysis (HD) patients. Our studies indicate that as Hct rises, dialyzer mass transport for some clinically critical solutes will be adversely affected. When whole blood clearances are corrected for solute-specific blood-water flows (QBH2O), the effect on the surrogate molecule, urea, used in urea kinetic modeling (UKM) is deceptively minimal, because only urea can diffuse almost instantly from red cells into blood water. For the critical solutes, potassium and phosphate, QBH2O is reduced to Q (plasma water). With a KoA of 690 ml/min at QB = 300, clearance of potassium falls at least 19.3% as Hct rises from 20 to 40% so that steady-state predialysis potassium could rise from 6.0 to 6.95 mEq/L. Already inadequate phosphate clearance falls at least 10% and additional loss results from physical interference by RBCs with solute diffusion. Hcts are further increased with rapid weight losses during high-efficiency dialyses (0.15 per 5% weight loss in 3 hours, r = 0.82) resulting in blood-side pressures such that most dialysis machines cannot provide adequate dialysate pressures to maintain low ultrafiltration rates (UFRs) at the high QB levels. The combination of pre-existing diffuse vascular disease, postdialysis hypovolemia, hypotension, decreased cardiac output, and increased blood viscosity has and will produce disastrous syndromes of organ ischemia, thrombosis, and infarction. Predialysis hypertension can worsen. Extreme caution and adjustment of dialysis regimen is necessary as patient Hct rises above 36%.
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PMID:Erythropoietin alert: risks of high hematocrit hemodialysis. 319 6


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