摘要:

In addition to preserving the permselectivity of the vascular wall and providing an antithrombogenic surface, the vascular endothelium contributes importantly to the regulation of vasomotor tone. Indeed, the endothelium participates in the conversion of angiotensin I to angiotensin II; the enzymatic inactivation of several plasma constituents such as bradykinin, norepinephrine, serotonin, and ADP; and the synthesis and release of vasodilator substances such as prostacyclin and the recently discovered endothelium-derived relaxing factor (EDRF). The diffusible EDRF released from the endothelium is nitric oxide or a substance closely related to it such as nitrosothiol. The endothelium also synthesizes and releases vasoconstrictive factors, including products derived from arachidonic acid metabolism and the recently discovered peptide endothelin. An increasing body of evidence from experimental and clinical studies indicates that EDRF and endothelium-derived contracting factors play an important role in vascular physiology and pathology. It has become apparent that the balance of these factors may be a major determinant of systemic and regional hemodynamics. Moreover, through generally opposite effects on growth-related vascular changes, contracting factors such as endothelin and relaxing factors such as EDRF also may be important determinants of the vascular response to injury in various disease states such as atherosclerosis and hypertension. It is clear that the vascular endothelium is a complex and dynamic organ. Understanding endothelium function in normal physiology and disease states is of potential clinical importance and should be the focus of future investigation.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Recent studies suggest that humoral and endothelium-dependent mechanisms may play an important role in the cerebral circulation. Angiotensin may acutely and chronically increase resistance of large cerebral arteries and reduce cerebral microvascular pressure without changing cerebral blood flow. We hypothesize that the brain may sense reductions in microvascular pressure and initiate compensatory neurohumoral responses to raise arterial pressure. Vasopressin appears to play an important role in regulation of production of cerebrospinal fluid and brain fluid volume. Vasopressin also may be protective when intracranial pressure is elevated. Endothelium-dependent mechanisms also may have important influences on tone of cerebral vessels. Synthesis of the endothelium-derived relaxing factor nitric oxide, or a nitric oxide-containing compound, appears to influence both basal tone and responses of large cerebral arteries to acetylcholine in vivo. Large cerebral arteries dilate in response to increased blood flow in vivo, and this response may be mediated in part by release of a humoral factor by endothelium. Endothelium-dependent responses of cerebral arterioles to receptor- and nonreceptor-mediated agonists are impaired during chronic hypertension. The mechanism of impairment of endothelium-dependent responses of cerebral arterioles appears to involve production of an endothelium-derived contracting factor. (Hypertension 1991;17:917-922)

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

In previous reports, we described the isolation and characterization of an endogenous digitalislike factor (EDLF). In this report, we describe a unique combination of bioassay and large-scale purification methodology that made possible the purification of sufficient quantities of this inhibitor of Na+,K+-ATPase for structural analysis. Using an initial XAD-2 extraction and preparative high-performance liquid chromatography followed by a batch enzyme affinity extraction and two subsequent semipreparative chromatographic steps, 300 1 of human plasma was processed, yielding 31 /tg (53 nmol) of pure EDLF and representing purification on a dry weight basis in excess of 0.6 billionfold. Four divergent pieces of evidence, including chromatographic, mass spectrometric, immunoreactive, and binding characteristics, suggested that the EDLF purified in the present study was either ouabain or an isomer of ouabain. This material may represent a plasma-borne, naturally occurring, selective, high-affinity ligand for the digitalis binding site that may play a significant role in the modulation of the sodium pump and thereby cellular electrolyte homeostasis in humans. {Hypertension 1991;17:923-929)

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A sodium pump inhibitor has been isolated from human plasma and extensively purified. This material, endogenous digitalislike factor, was examined by a variety of mass spectrometric techniques. A low-resolution fast atom bombardment mass spectrometric analysis of a sample of purified endogenous digitalislike factor revealed a single unique molecular ion in the mass range 100-2,500. The accurate mass was determined to be 585.295 Da in a second highresolution fast atom bombardment mass spectrometric experiment Based on this accurate mass, the elemental composition of endogenous digitalislike factor was determined and found to be identical to the elemental composition of the known cardenolide ouabain. Direct comparison of ouabain and endogenous digitalislike factor by linked scan tandem mass spectrometry, derivatization with acetic anhydride coupled with fast atom bombardment mass spectrometry, and analytical high-performance liquid chromatography failed to reveal any differences. We conclude that the endogenous digitalislike factor isolated from human plasma is ouabain or a closely related isomer. (Hypertension 1991;17:930-935)

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Recently, attempts to purify and identify a circulating inhibitor of the sodium pump have been successful. Based on the outcome of mass spectral analysis of purified inhibitor, we raised in rabbits antibodies to conjugates of the commercially available cardenolide ouabain and used them in the development of an indirect enzyme-linked immunosorbent assay (ELISA) for endogenous digitalislike factor (EDLF). Antisera obtained were of high antibody titer (l:2xlO6) and showed full cross-reactivity with purified EDLF. The antisera were highly specific for ouabain and structurally related cardenolides but showed no cross-reactivity with numerous endogenous steroids and peptides. At each step in the purification of EDLF, inhibition of the sodium pump and immunologic cross-reactivity were inseparable. The ELISA as developed had a working range of 5-2,000 fimol, with an IC50 of 80 fmol/well. Using solid-phase extraction and the ELISA, we determined the circulating level of EDLF in plasma from normal human volunteers to be 138±43 fmol/ml, whereas patients on total parenteral nutrition for at least 1 week had a circulating level of 108 ±17 fmol/ml, suggesting that the circulating factor was of endogenous origin. The ELISA developed appears to measure a naturally occurring counterpart to the cardenolides that could play a role in modulating the sodium pump and thereby cellular electrolyte homeostasis. (Hypertension 1991;17:936-943)

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

An endogenous ouabainlike compound (OLC) has been purified from human plasma, and mass spectrometry has shown it to be indistinguishable from plant-derived ouabain. This human OLC was tested for its effects on evoked tension in guinea pig left atria and aortic rings. The tissues were incubated at 37°C in bicarbonate-buffered physiological salt solution gassed with 95% O]-5% CO2. In atria stimulated electrically at 1 Hz, 85 and 170 nM human OLC increased peak active force to 177±15% and 313±32% of control, respectively (n=3), with little effect on the duration of contraction. On washout of the OLC, peak systolic force returned to the control level with a half-time of 4.3 ±0.5 minutes. Similar results were obtained with 160 nM plant-derived ouabain: peak systolic force increased to 310±31% of control (n=4) and returned to the control level with a half-time of 3.8 ±0.2 minutes during washout In aortic rings, neither 170 nM human OLC nor 160 nM plant ouabain (30-minute treatments) affected resting (unstimulated) tension, but they increased the contractions evoked by histamine (0.2-1.0 /μM) to 156±13% (n=4) and 143±6% (n=4) of control responses, respectively. The mean half-time for washout of the OLC and plant ouabain-induced augmentation of histamine-evoked tension exceeded 35 minutes. These data show that human OLC has cardiotonic and vasotonic actions qualitatively and quantitatively similar to those observed with plant ouabain. Together with data on the mass spectrometry, chromatographic characteristics and interaction with Na+,K+-ATPase, and full cross-reactivity with polyclonal anti-ouabain antibodies, these physiological findings support the view that human OLC is ouabain.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To investigate the cellular basis linking hypertension, non-insulin-dependent diabetes melllrus (NIDDM), and obesity, we used31P and19F nuclear magnetic resonance spectroscopy to measure intracellular pH (pHJ, free magnesium (M&), and cytosolic free calcium (Ca1) in erythrocytes of obese and NIDDM subjects with and without hypertension. Compared with nonnotensive, nondiabetic controls (Ca125.2 ±1.4 nM; Mg1232 ±8 μM), Cat was elevated in both nonnotensive (36.8±2.7 nM, sig=0.005) and hypertensive (43.4±2.9 nM, sig=0.001) NIDDM subjects, and Mg1was concomitantly suppressed (nonnotensive: 206±ll μM, sig=0.05; hypertensive: 196±8 μM, sig=0.001). Similar but less striking changes were noted in obese subjects. Values of pH, were significantly lower (sig=0.05) in all hypertensive groups compared with their nonnotensive controls. Continuous relations were observed for all subjects between Ca1, and diastolic blood pressure (r=0.649,/7<0.001) and body mass index (r=0-565,p<0.001), between Mg, and diastolic blood pressure (r=-0.563,p<0.001) and fasting blood glucose (r=-0.580,p<0.001), and in diabetics, between pH1and diastolic blood pressure (r= -0.680,p<0.001). Thus, the constellation of elevated Ca1, and suppressed Mg1and pH1levels is characteristic of the hypertensive state. These abnormalities of cellular ion handling in whole or in part common to hypertension, diabetes, and obesity may contribute to the pathophysiology of these syndromes and may help to explain their frequent clinical coexistence.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Some fatty acids are potent inhibitors of angiotensin binding and aldosterone production in adrenal glomerulosa cells and thereby may be involved in regulating salt and water balance. To study the possible regulation of fatty acids by salt, we measured the levels of unesterified fatty acids in plasma from patients subjected to extremes of dietary salt intake and saline infusion. Insulin and catecholamines, two known regulators of plasma fatty acids, also were measured. Infusion of 2 1 saline over 4 hours caused the levels of most unesterified fatty acids to rise. Total unesterified fatty acids rose 60-100%. A high salt diet caused a smaller rise in total unesterified fatty acids (approximately 33%). In both instances, oleic and palmitoleic acids showed the greatest proportionate increases, whereas stearic acid was relatively unaffected. When salt loads were administered by either intravenous or dietary routes, plasma insulin levels fell by approximately 50%. Plasma norepinephrine increased after saline infusion but not during a high salt diet Postsaline levels of fatty acids correlated inversely with postsaline levels of aldosterone, supporting a possible role for fatty acids as physiological regulators of the adrenal glomerulosa. A rise in plasma fatty acids and fall in insulin in response to salt loads could act in concert to increase sodium excretion, constituting a physiological mechanism contributing to salt and water balance.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To investigate the effects of a low calorie regimen on sympathetic function and its relation to blood pressure response, 22 untreated obese essential hypertensive patients (50±2 years, body mass index 29 ±1 kg/m2) were hospitalized and a diet was prescribed of 2,000 kcal/day for 5 days (control period) followed by 800 kcal/day for 21 days without changing salt intake (8-10 g/day). The dose of intravenous phenylephrine infusion needed to elevate systolic blood pressure 20 mm Hg (CD20) and the 24-hour urinary excretion of norepinephrine (UNE) were measured. During the low calorie period, blood pressure normalized in 14 patients (responder group, 124±3/79±4 mm Hg) and eight remained hypertensive (poor responder group, 158±6/103±3 mm Hg). At the control period, blood pressure and body mass index were similar, but the responder group had higher UNE(134±15 μ/day) and CD20(127±11 μg) than the poor responder group (89±6 μ/day and 79±13 μ, respectively). During the low calorie period, both UNE(87±15 μg/day) and CD20(74±10 μ) decreased in the responder group; no change was seen in the poor responder group. Changes in UNE and systolic blood pressure were correlated (r=0.6,p<0.05). In conclusion, suppression of sympathetic activity plays a role in blood pressure reduction during moderate caloric restriction.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A prospective study on 1,482 adult members of 98 Utah pedigrees was carried out to determine which variables may be associated with an increased risk of hypertension incidence. After an average of 7 years of follow-up, 40 individuals had been placed on antihypertensive medications to lower blood pressure. Baseline study variables included anthropometries, clinical chemistry measurements of blood and urine, socioeconomic and lifestyle variables, and detailed erythrocyte ion transport and concentration measurements. Age (relative risk of 4.28 for a 2 SD difference,p< 0.0001) and baseline systolic and diastolic blood pressures (relative risks of 3.55 and 3.52, respectively, bothp< 0.0001) had the strongest associations with hypertension incidence. Controlling for age and baseline blood pressure, the following age- and sex-adjusted variables were associated with an increased risk of future hypertension (relative risks for a 2 SD difference, all /?<0.10): family history of hypertension (2J5); height (1.97); body mass index (2.31); abdominal girth (2.66); subscapular, suprailiac, and triceps skinfold thicknesses (2.79, 2.52, and 2.28, respectively); percent ideal body weight (2.63); log triglyceride concentration (2.02); plasma uric acid (2.16); inorganic phosphate (0.50); and passive erythrocyte sodium permeability (1.59). The final model, which included all of the age- and sex-adjusted variables (p<0.10) in a backward elimination logistic regression analysis, consisted of age (4.78), systolic blood pressure (2.91), subscapular skinfold thickness (2.21), height (1.92), uric acid (2.06), inorganic phosphate (0.50), and family history of hypertension (1.82). None of the ion transport or concentration measurements was associated with an increased risk of hypertension. We conclude that the risk factors of age, body fat and size, plasma uric acid, low plasma inorganic phosphate, and family history of hypertension, previously shown to be significant in crosssectional studies, prospectively increase the risk of hypertension. If other variables have important predictive roles, then they may affect only a subset of this or other large study populations.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID