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

Ouabain-like factor (OLF) has been implicated to play an important role in certain forms of hypertension. We isolated OLF from the urine of salt-loaded healthy subjects by stepwise chromatographic procedures. The post-salt fraction (F IV) eluted from Sephadex G-25 was rechromatographed on Sephadex G-10. A late small-molecular-weight fraction F8 inhibited Na-K-ATPase in vitro (OLF activity). The effects of OLF on intracellular Ca2+ concentrations ([Ca2+]i) and pH (pHi) were examined in cultures of vascular smooth-muscle cells using the fluorescent probes fura-2 and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF), respectively. Preincubation with OLF increased basal [Ca2+]i from 87 +/- 6 to 160 +/- 8 nM (p < 0.001) and enhanced arginine vasopressin-stimulated maximal [Ca2+]i (418 +/- 11 vs. 523 +/- 14 nM, p < 0.01). This effect was similar to that of ouabain. OLF also induced a rapid transient increase of [Ca2+]i (82 +/- 9 vs. 253 +/- 23 nM, p < 0.01); [Ca2+]i returned to levels slightly above baseline within approximately 4 min. OLF-stimulated [Ca2+]i was attenuated by verapamil (126 +/- 5 nM, p < 0.01) and was also reduced in Ca(2+)-free medium (104 +/- 9 nM, p < 0.01). As opposed to OLF, ouabain did not exhibit this fast transient effect on [Ca2+]i. Amiloride (10(-3) M) blocked the sustained effect of OLF on [Ca2+]i (77 +/- 11 vs. 86 +/- 12 nM, NS). OLF induced an increase of pHi from 7.09 +/- 0.03 to 7.28 +/- 0.04 (p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cellular mechanisms of action of a ouabain-like factor in vascular smooth-muscle cells. 750 17

The mitogenic effect of a low-molecular-weight, Na+,K(+)-ATPase inhibitory factor isolated from bovine hypothalamus and hypophysis (hypothalamic hypophysary inhibitory factor, HHIF) and ouabain on cultured rat mesangial cells was examined. Ouabain induced a potent stimulation of the [3H]thymidine incorporation to DNA, ranging from threefold for a dose of 10(-7) M to seven times for 10(-5) M. The amount of proteins per well also increased in a dose-dependent way, which was already significant from basal values for the lower dose used. HHIF also induced a dose-dependent stimulation of [3H]thymidine incorporation into DNA, ranging from 1.7 times for a concentration of 0.02 U/ml to 4.5 times for the concentration of 2 U/ml. The amount of protein per well also increased with HHIF, but the increase was significant only for the higher dose used. These data allow us to conclude that HHIF could play a role in the vascular hypertrophy that is associated with the pathogenesis of hypertension.
 ...
PMID:Effect of ouabain and hypothalamic, hypophysary inhibitory factor on rat mesangial cell proliferation. 750 23

Ouabain-like factor (OLF) has been extracted from hypothalamus and adrenal glands of the ox and rats of the Milan hypertensive strain (MHS) and their normotensive controls (MNS). OLF was identified by its ability (a) to inhibit ouabain-sensitive 86Rb uptake into human erythrocytes, (b) to displace [3H]ouabain binding, and (c) to inhibit purified dog kidney Na-K-ATPase. Rat and bovine OLF have similar characteristics. Those that are close to ouabain are (a) ligand conditions for maximal inhibitory activity, (b) high-performance liquid chromatography retention time, (c) reversibility of inhibitory activity on Na-K-ATPase, (d) reduced Na-K-pump inhibitory activity by K+, (e) high affinity for Na-K-ATPase, and (f) no activity on Ca(2+)-ATPase. OLF does not resemble ouabain because the capacity of OLF to inhibit ouabain low-affinity Na-K-ATPase isoform is greater than that of ouabain. The yield of OLF is greater from MHS than MNS hypothalamic and adrenal extracts. These findings represent the first direct evidence that a higher amount of OLF is present in tissues from genetically hypertensive rats than from their inbred normotensive controls, maintained under the same dietary and environmental conditions. This further supports previous observations on the role of OLF in the pathogenesis of MHS hypertension.
 ...
PMID:Characteristics of a ouabain-like factor from Milan hypertensive rats. 750 36

To assess whether chronic ouabain administration causes hypertension by increasing sympathetic activity, we recorded arterial blood pressure and heart rate at rest and after ganglionic blockade in conscious Wistar rats following 10 to 14 days of central or peripheral administration of ouabain. Intracerebroventricular or intravenous infusion of ouabain (10 micrograms/d for both) as well as subcutaneous ouabain pellets (releasing 25 micrograms ouabain/d per pellet) increased mean arterial pressure by 20 to 30 mm Hg and heart rate by 40 to 60 beats per minute. Ouabain pellets increased blood pressure and heart rate in a dose-related manner. After 2 weeks of all ouabain treatments, ouabainlike activity in plasma was not changed but increased significantly in hypothalamus and adrenals. Ouabainlike activity in the adrenals was increased more by intravenous than subcutaneous or intracerebroventricular ouabain treatment, but the different treatment modes caused similar increases in the hypothalamus. Concomitant central infusion of antibody Fab fragments against ouabain prevented the ouabain pellet-induced increases in blood pressure and heart rate. Ganglionic blockade by intravenous hexamethonium normalized blood pressure and heart rate in ouabain-treated rats. These data suggest that in normotensive rats exogenous ouabain, regardless of the mode of administration, may act centrally to cause sympathoexcitation and thus hypertension.
Hypertension 1994 Jun
PMID:Chronic central versus peripheral ouabain, blood pressure, and sympathetic activity in rats. 791 50

We investigated the mechanisms underlying the insulin-induced attenuation of sympathetic forearm vasoconstriction in healthy humans. In 5 subjects, we applied 20 mm Hg lower body negative pressure for 30 minutes in control conditions and during a 60-minute infusion of insulin (0.05 mU/kg per minute) in the brachial artery and measured forearm norepinephrine kinetics and hemodynamics. In 11 subjects, we applied graded lower body negative pressure at 5, 10, 15, and 20 mm Hg for 5 minutes each in control conditions and during the simultaneous intrabrachial administration of insulin (0.05 mU/kg per minute) (5 subjects) or insulin plus ouabain (3.5 micrograms/min per liter) (6 subjects) to investigate whether insulin acts through a potentiation of the vascular smooth muscle Na+,K(+)-ATPase. To assess a possible effect of insulin on a specific adrenergic receptor pathway, in a further study group we evaluated (1) the forearm vascular response to intrabrachial infusion of the alpha 1-adrenergic receptor agonist phenylephrine (0.5, 1, and 2 micrograms/kg per minute; n = 7) and of the alpha 2-adrenergic receptor agonist BHT-933 (0.5, 1, 2, and 4 micrograms/kg per minute; n = 9), and (2) the effects of intra-arterial infusion of prazosin (0.5 microgram/100 mL per minute) alone or combined with insulin on the forearm vascular response to graded lower body negative pressure (7 subjects). Insulin blunted the peak increase in forearm vascular resistance (from 13 +/- 2 to 6 +/- 2 U, P < .05) but not the rise in forearm norepinephrine spillover induced by 20 mm Hg lower body negative pressure (from 8.3 +/- 1.8 to 11.1 +/- 3.5 pmol/min per liter, P = NS). Ouabain administration did not prevent the insulin-induced attenuation of the forearm vasoconstrictive response to graded lower body negative pressure. Insulin infusion in the brachial artery did not modify the forearm vasoconstriction induced by intra-arterial infusion of phenylephrine but significantly reduced the increase in forearm vascular resistance induced by BHT-933 (F = 6.111, P < .001). Finally, intra-arterial infusion of prazosin significantly attenuated the forearm vasoconstriction induced by graded lower body negative pressure. The residual vasoconstrictive response was abolished by insulin infusion. Taken together, these findings suggest that insulin interacts with the sympathetic nervous system at the vascular level predominantly through the alpha 2-adrenergic vasoconstrictive pathway.
Hypertension 1994 Oct
PMID:Insulin blunts sympathetic vasoconstriction through the alpha 2-adrenergic pathway in humans. 791 34

Ouabain has recently been reported to be an endogenous mammalian substance released by the adrenal cortex and present in normal plasma. We have attempted to confirm and extend this observation. Using a ouabain radioimmunoassay developed in this laboratory, we fractionated by high-performance liquid chromatography (HPLC) normal human plasma from healthy volunteers to determine the presence of ouabain immunoreactivity and compare this immunoreactivity with authentic ouabain. In most subjects no ouabain immunoreactivity that coeluted with authentic ouabain was observed. Some subjects had ouabain-immunoreactive material present at low levels, but it was largely attributable to cross-reactivity with diverse substances found not to be ouabain. Similar results were obtained after analysis of plasma collected from 10 patients entering a medical intensive care unit. Studies of serum-free medium conditioned by bovine adrenocortical cells showed some ouabain immunoreactivity. To determine whether this material might be a steroid product of cholesterol side-chain cleavage, we performed chemical blockade of steroidogenesis, which effectively suppressed progesterone production by these cells but had no consistent effect on ouabain immunoreactivity in this medium. Stimulation of steroidogenesis with 22-R-OH-cholesterol in bovine adrenocortical cells did not produce any increase in the ouabain immunoreactivity present in conditioned medium. Subsequent HPLC studies of ouabain immunoreactivity in bovine adrenocortical cell-conditioned medium indicated that authentic ouabain did not account for most of the ouabain immunoreactivity in serum-free medium. Studies with bovine adrenocortical cells incubated in a minimal salt and glucose medium indicated a small peak of immunoreactivity that may correspond to authentic ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 May
PMID:Is ouabain an authentic endogenous mammalian substance derived from the adrenal? 796 26

We have investigated the effects of L-NG-nitro arginine (L-NOARG), glibenclamide, ouabain, tetraethylammonium and 4-aminopyridine on the methacholine-induced endothelium-dependent vasodilation in perfused resistance arteries from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Since the concentration-response curves of MCh were similar in both types of preparations there does not seem to exist an endothelial dysfunction in mesenteric arteries of SHR. L-NOARG only partially inhibited the maximal methacholine-induced response in preparations taken from SHR and WKY rats. Ouabain decreased the maximal effect of methacholine without altering the potency (pD2). Preparations from SHR were more susceptible to ouabain. 4-aminopyridine and tetraethylammonium decreased the pD2 for methacholine without reducing the maximal effect (Emax). The WKY rat preparations were more affected by these compounds. An important role of ATP-sensitive potassium channels may be ruled out since glibenclamide was without effect on the methacholine-induced vasodilation. It is concluded that endothelium-derived relaxing factor is only partially responsible for the endothelium-dependent vasodilation. Indirect arguments point toward a role of endothelium-derived hyperpolarizing factor, since ouabain, tetraethylammonium and 4-aminopyridine inhibited the methacholine-induced response. Although hypertension related differences for these compounds were observed high blood pressure does not seem to alter the functional response to muscarinic stimulation.
 ...
PMID:The role of nitric oxide and potassium channels in endothelium-dependent vasodilation in SHR. 820 19

Chronic parenteral administration of ouabain to normal rats raises plasma ouabain concentrations to low nanomolar levels and induces hypertension [C. M. Yuan, P. Manunta, J. M. Hamlyn, S. W. Chen, E. Bohen, J. Yeun, F. J. Haddy, and M. B. Pamnani. Hypertension 22: 178-187, 1993 and see also M. P. Blaustein. Am. J. Physiol. 264 (Cell Physiol. 33): C1367-C1387, 1993]. To determine whether rat arteries are sensitive to these low ouabain levels, we tested the effects of various ouabain concentrations on caffeine-evoked contractions (CEC) in rat aortic and small mesenteric artery rings. CEC amplitude was used as a measure of the sarcoplasmic reticulum (SR) Ca2+ content. Ouabain increased CEC in aortic as well as mesenteric artery rings, but the effects in the aorta were difficult to quantitate because the CEC were often oscillatory. Mesenteric artery, under control conditions and after sensitization with 10-30 nM phenylephrine (PE), exhibited biphasic ouabain dose-CEC response curves. Low concentrations of ouabain (0.1-10 nM) caused small significant increases in CEC, but a further effect was observed only with > or = 10 microM ouabain. PE shifted the ouabain dose-response curve toward lower ouabain concentrations; conversely, ouabain shifted the PE dose-response curve toward lower PE concentrations. It appears that nanomolar concentrations of ouabain can influence vascular responsiveness to vasoconstrictors. We conclude that rat vascular smooth muscle contains both high- and low-affinity ouabain receptors, possibly corresponding to Na+ pumps with alpha 3- and alpha 1-subunit isoforms, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nanomolar ouabain augments caffeine-evoked contractions in rat arteries. 823 91

The purpose of the present study was to examine alterations in membrane fluidity of erythrocytes in essential hypertension by means of an electron paramagnetic resonance (EPR) and a spin labeling method. In addition, we investigated the effects of ouabain on the fluidity of erythrocytes, and elucidated a possible role of Na+, K(+)-ATPase in the regulation of membrane fluidity in hypertension. Erythrocytes obtained from patients with essential hypertension were examined compared with those from age-matched normotensive subjects. The EPR spectra for 5-nitroxide stearate incorporated into erythrocyte membranes were studied. The values of the outer hyperfine splitting and order parameter (S) of the EPR spectra were significantly higher in patients with essential hypertension than in normotensive subjects. This finding shows that the membrane fluidity of erythrocytes might be lower in essential hypertension. Ouabain-loading of erythrocytes decreased the membrane fluidity (S value was increased). The ouabain-induced changes were significantly greater in essential hypertension than in normotensive subjects. These results demonstrate that the membrane fluidity of erythrocytes might be lower in essential hypertension than in normotensive subjects. Furthermore, the membrane fluidity might be highly dependent on the Na+, K(+)-ATPase activity in essential hypertension, which would suggest an abnormality in Na(+)-related cellular functions in hypertension.
 ...
PMID:Membrane fluidity of erythrocytes and its modulation by ouabain in essential hypertension--an electron paramagnetic resonance study. 828 19

The influence of endothelium on the neurogenic component of ouabain-induced contractions in isolated perfused guinea pig carotid arteries was analyzed. Ouabain (0.1 mumol/L to 0.1 mmol/L) evoked concentration-dependent increases of perfusion pressure. Phentolamine (0.3 to 10 mumol/L) and prazosin (30 nmol/L to 10 mumol/L) (nonselective antagonist of alpha-adrenergic receptors and selective antagonist of alpha 1-adrenergic receptors, respectively) induced a concentration-dependent relaxation in segments precontracted with ouabain (0.1 mmol/L). When the arteries were preincubated with those blockers (both at 3 mumol/L) or the animals were pretreated with reserpine, the contractions to the glycoside were diminished, indicating that they are partially mediated by norepinephrine release from adrenergic nerve endings. De-endothelialization abolished the effect of adrenergic blockade on ouabain-induced contractions. On the other hand, de-endothelialization did not modify significantly the effect of the adrenergic blockade on norepinephrine-induced contractions. The nitric oxide blocker oxyhemoglobin, at concentrations (10 mumol/L) that abolished endothelium-dependent relaxations induced by 3 mumol/L acetylcholine; or the cyclooxygenase blocker indomethacin (10 mumol/L) did not modify the relaxation caused by phentolamine. In bioassay experiments, 30 mumol/L phentolamine induced a relaxation on the ouabain-elicited contraction only when the glycoside was added through a donor segment with endothelium. Ouabain-induced tritiated norepinephrine release was significantly reduced by the removal of endothelium but not by 1 mumol/L oxyhemoglobin or 1 mumol/L indomethacin. These results suggest that the endothelium modulates the neurogenic component involved in contractions evoked by the glycoside by a diffusible factor (or factors) whose nature is unknown; however, the factor is neither nitric oxide nor a cyclooxygenase-related compound.
Hypertension 1994 Jan
PMID:Neurogenic component of ouabain-evoked contractions is modulated by the endothelium. 828 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>