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

The renin-angiotensin system appears to play a major role in the regulation of sodium excretion and fluid intake in a wide variety of animal species from mammals to teleosts. In mammals the system has evolved further importance in terms of blood pressure homeostasis. This hormonal system in all species appears to involve a serum protein prohormone, angiotensinogen, a proteolytic enzyme, renin, and angiotensin I, the decapeptide product of the reaction between renin and angiotensinogen. The importance of this system to the organism appears to correlate directly with the necessity to conserve sodium while an abnormality of this process may underlie the development of hypertension in man. As the starting point of the system, angiotensinogen assumes special importance as a possible index of evolutionary development. In addition, it has been known for many years that human (viz. primate) angiotensinogen differs from that found in other mammals in its inability to be a substrate for animal renins while animal angiotensinogens readily react with human renin. Thus, the enzymatic specificity appears to reside with the prohormone. The biochemical basis for this difference is unresolved due primarily to the lack of purified human angiotensinogen. In this paper we describe methods for the purification of human angiotensinogen which have direct applicability to animal angiotensinogens. Our approach utilizes ammonium sulfate precipitation, Sephadex G-150 chromatography, multiple isoelectric focusing, and concanavalin A-Sepharose affinity chromatography. With the availability of highly purified human angiotensinogen we compared the molecular weights, heterogeneity, isoelectric points, and thermal lability of hog, rabbit, and human angiotensinogen in order to define the biochemical basis of the species variation in renin reactivity...
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PMID:Human angiotensinogen. Purification partial characterization, and a comparison with animal prohormones. 1 60

The phenomenon of plasma renin activattion by acid dialysis and preincubation with trypsin was studied in normal human plasma. Activation of plasma renin by exposure to pH 3.3 was shown to require at least one dialysis step and could be inhibited by the presence of Trasylol, indicating the involvement of a protease in acid activation. Amniotic fluid exposed to pH 1.5 to destroy renin and renin substrate was also found to contain an enzyme capable of activating plasma renin. The Michaelis-Menten constant Km and the molecular weight of activated "renin" were found to be similar to those of normal plasma renin. Inactive renins or renin-like enzymes were partially purified from plasma by affinity chromatography on concanavalin A, precipitation with (NH4)2SO4 and isoelectric focusing. Trypsin and acid exposure gave similar results with regard to the activation of this zymogen, suggesting that trypsin and acid dialysis may increase plasma renin activity by the same mechanism.
Hypertension
PMID:Studies on renin activation in normal human plasma. 9 12

The bioelectrical activity of the aortic nerve was studied in normal rabbits and in those with experimentally induced hypertension. Electroneurograms of the aortic nerve of rabbits with renal and coarctational (stenosis of the abdominal aorta) hypertension demonstrated the same burst-like activity synchronous with the systolic contractions of the heart that was noted in normotensive animals. The threshold of the transit of the burst-like activity of the aortic nerve into the uniform one in cases of acutely elevated arterial pressure (induced by injections of noradrenalin and angiotensin) and the threshold of the disappearance of the mentioned activity after an acute reduction of the arterial pressure (induced by injections of acetylcholine, tetra-ethylammonium or by acute bleeding) in rabbits with renal and coarctational hypertension are shifted upwards, as compared to those in normotensive rabbits. It is the more true of the former threshold. The depressor reaction to the administration of the ganglionic blocker -- tetra-ethyl-ammonium -- in renal hypertension during the initial 2 months of the disease remains unchanged, with the exception of the 4th and 8th weeks, when it is elevated. It is concluded that the baroreceptors of the aortic arch percept the chronically elevated arterial pressure as a normal one reacting adequately to its acute changes in either direction. Thanks to this the barorecptors of the aortic arch strive to maintain a high level of the arterial pressure and provide for a stabilization of hypertension.
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PMID:[Functional state of baroreceptors of the aortic arch in experimental hypertension]. 119 46

In 45 patients with chronic compensated hypertensive glomerulonephritis and in 184 others suffering from different clinical variants of the same disease the state of tubular functions controlling the osmotic and acid-base homeostasis was investigated. The objective was to assess in this connection the scope of renal processes in this connection the scope of renal processes peculiar to the hypertensive from that keep up these function, to reveal (by studying the materials of renal biopsies) the morphological substrate of the dysfunctional under consideration and also to determine its ossible importance in maintaining hypertension. As a criterion for the mass of active nephrons the magnitude of glomerular filtration (from clearance of endogenous creatinine with a minute-long diuresis of 1.5-2.5 ml/min) was used. It was established that, as distinct from the latent forms, in cases of benign hypertensive form of chronic glomerulonephritis, as well as in those of nephritic one, the ammonium excretion is halved and so is also the maximum osmotic concentration. Common to the hypertonic syndrome proved to be a particularly steep, by 70%, fall of CH2O. The disclosed disturbances, except for reduced excretion of "osmotically free" water, may be attributed to the nature of morphological changes inherent in this form of the disease, i.e. in the atrophy of the tubular epithelium and of the tubulo-interstitial component. The major fall of CH2O is largely determined by an increased proximal transport of sodium and inhibition of this process in the distal part of the nephron. A derangement of the studied tubular functions may, though in part, be considered as a factor keeping up the arterial pressure.
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PMID:[Tubular functions in the regulation of osmotic and acid-base homeostasis in chronic hypertensive compensated glomerulonephritis]. 123 22

Investigations covered 64 women in the III trimester of pregnancy. In this group 34 were with diagnosed primary arterial hypertension (examined group), and 30 were apparently healthy (control group). In both groups the blood serum concentrations of creatinine, urea, uric acid and electrolytes were determined. Creatinine clearance and acid-base balance were determined in these cases also. In 24 hours urine samples the NH4+, H+, Na+ and K+ ions concentrations were established. Impaired kidney function was shown in the patients from the examined group.
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PMID:[Kidney function in pregnant women with primary arterial hypertension]. 130 10

In 53 pregnant patients in the III trimester of pregnancy kidney function investigations were carried. The group consisted of 23 patients with chronic kidney diseases with superimposed arterial hypertension (examined group) and of 30 healthy pregnant women (control group). In the examined group an increase of blood-serum urea, uric acid and creatinine concentrations were demonstrated. In these women the blood pH was decreased also. The urinary excretion of NH4+ and H+ ions was decreased, the excretion of Na+ and K+ was normal.
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PMID:[Kidney function in pregnant women with hypertension in the course of chronic kidney disease]. 130 11

Dipeptidyl peptidase IV (EC 3.4.14.5) and angiotensinase A (EC 4.4.11.7) were purified to homogeneity from pooled urine concentrate of patients with renal damage, using ultrafiltration, ammonium sulphate precipitation, lectin affinity chromatography, FPLC-ion-exchange(Mono-Q-)chromatography, and FPLC-gel filtration (Superdex). Based on the specific enzyme activity of the starting material, dipeptidyl peptidase IV was enriched 1629 fold, angiotensinase A 1183 fold. The relative molecular masses, Michaelis constants and isoelectric points were determined. Negative staining of the purified enzymes revealed globular proteins (5-7 nm). Antisera raised against dipeptidyl peptidase IV and angiotensinase A reacted specifically with tubular and, in the case of anti-angiotensinase A sera, with tubular and glomerular structures. In addition, urinary membrane vesicles of proximal tubule origin were eluted with the void volume (Superdex-gel filtration), indicating heavy epithelial cell disintegration. Both soluble tissue enzymes (dipeptidyl peptidase IV, angiotensinase A) and vacuolar blebs shed from epithelia contribute to proteinuria, as was shown in patients with glomerulonephritis, interstitial nephritis, diabetic nephropathy and, for angiotensinase A, in patients with essential arterial hypertension.
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PMID:Biochemical and immunological properties of urinary angiotensinase A and dipeptidylaminopeptidase IV. Their use as markers in patients with renal cell injury. 136 94

Hypertrophy of vascular smooth muscle cells (VSMC) is a pathogenic feature of hypertension which may contribute to abnormal vessel tone and function. As a consequence of the increase in cell size associated with hypertrophy, it is likely that alterations in the mechanisms that regulate VSMC intracellular volume occur. Because the Na+/H+ exchanger plays an important role in volume regulation and because we previously observed long term alterations in Na+/H+ exchange and pHi in response to angiotensin-II-induced (ang II) hypertrophy, we studied cell-acidifying mechanisms. To do this, we measured alkaline recovery from NH4Cl-mediated alkalinization, using the fluorescent dye, 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein. VSMC were growth-arrested (0.4% calf serum for 24 h) or hypertrophied (100 nM ang II in 0.4% calf serum for 24 h). Ang II-treated cells exhibited a 107% increase in alkaline recovery over control cells (13.86 +/- 1.87 versus 6.68 +/- 1.01 mmol H+/min/liter cells). The increase in alkaline recovery was not a result of increased Cl-/HCO-3 exchange becaue it was not HCO-3 dependent nor inhibited by 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid. Studies with bumetanide and the sterically inhibited substrate N(CH3)4+ showed that the alkaline recovery was mediated by NH4+ transport via the Na/K/2Cl cotransporter. Ang II-treated cells exhibited a 334% increase in bumetanide-sensitive alkaline recovery over control cells (9.16 +/- 1.90 versus 2.11 +/- 1.46 mmol H+/min/liter cells). Ang II-treated cells also exhibited a 90% increase in bumetanide-sensitive 86Rb uptake over control cells. These findings demonstrate that Na/K/2Cl cotransport activity is specifically induced in ang II-hypertrophied VSMC and establish this transporter as a component of the hypertrophic growth response.
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PMID:The Na/K/2Cl cotransporter is increased in hypertrophied vascular smooth muscle cells. 156 72

Because of the known influence of the lipid bilayer on membrane transport systems, the characteristics of the bilayer from vascular smooth muscle and from platelets were studied in genetically hypertensive and in normotensive rats. Membrane microviscosity was measured by the degree of polarization of embedded fluorophores. Both the core of the bilayer in which diphenylhexatriene (DPH) was embedded and the surface in which the trimethyl-ammonium derivative of DPH (TMA-DPH) was embedded evidence a greater microviscosity (less fluid) in the hypertensive than in the normotensive rat. We had previously observed that monovalent cation fluxes were elevated in hypertension. We now observe that an increase in calcium concentration reverses both the elevated microviscosity and the increased cation fluxes. Conversely an increased incorporation of cholesterol in the membrane increases both the microviscosity and the cation fluxes. We hypothesize that the greater microviscosity of the lipid bilayer in hypertension constitutes a generalized defect of the matrix in which the transport proteins function. We further hypothesize that this defect is responsible for the multiple abnormalities of membrane transport systems and the increase in vascular reactivity that have been described in genetic hypertension.
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PMID:The primacy of membrane microviscosity in genetic hypertension. 181 55

Amlodipine is a long acting dihydropyridine calcium antagonist recently introduced for the treatment of angina and hypertension. In order to document its stability in vitro and to develop a pharmacokinetic model in rabbits, a new reversed-phase liquid chromatography (LC) assay with UV detection was developed. The method utilized a C18 column (250 x 4.6 mm i.d.) with a mobile phase composed of a mixture of methanol 0.04 M ammonium acetate-acetonitrile (38:38:24, v/v/v) containing 0.02% triethylamine (final pH 7.1). Under these conditions, the retention times of amlodipine and the internal standard desipramine were 10.6 and 12.9 min, respectively. Using 1 ml of plasma, sensitivity of the assay was 2.5 ng ml-1 at which the RSD was 11%. The standard curve was linear from 2.5 to 100 ng ml-1 (r2 = 0.990), and the mean RSD at this concentration range was 6.8%. The pharmacokinetic model was developed in rabbits which provides results similar to those in dogs, but at less expense. The assay was also applied to a stability study comparing amlodipine and nifedipine in pH 3 and pH 7 ammonium acetate buffers and in methanol. Amlodipine was considerably more stable than nifedipine under all conditions. Finally the assay was applied to a pharmacokinetic study in rabbits (n = 6) after a single 1 mg kg-1 intravenous dose. The mean half-life (t1/2) of amlodipine was 6.5 h, the systemic clearance (CL) was 4.8 l h-1 kg-1 and the apparent volume of distribution at steady state (Vdss) was 30.2 l kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liquid chromatography assay for amlodipine: chemical stability and pharmacokinetics in rabbits. 184 Jan 30


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