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)

MDL-899 is new phthalazine derivative which has been developed as a substitute for hydralazine, which has several undesirable effects, in the treatment of hypertension. The effects of MDL-899 on human lymphocyte functions are analyzed. This drug inhibited in a dose-related fashion the blastogenesis of lymphocytes upon PHA and Con A activation and down-regulated the activation of allogeneic mixed lymphocyte reactions (MLR). On the contrary the drug enhanced the activation of autologous MLR of non T/T type. This effect was five times higher on cells which carried the HLA DR 4 phenotype. The above reported observations suggest that MDL-899, as well as hydralazine, affects the in vitro responsiveness of human lymphocytes mostly in subjects with HLA-DR 4 phenotype. Whether the impact of MDL-899 on immune function gives rise to a lupus like syndrome is not known. For this reason further studies are warranted to assess its long-term in vivo effects.
 ...
PMID:The effects of a new phthalazine derivative (MDL 899) on human lymphocyte functions. 294 87

There was made an exercise test until appearing exercise limiting symptoms in 50 patients with the second period of primary arterial hypertension (PAH) and in 73 healthy subjects. Exercise test was positive in 26 PHA patients (group I), and was negative in 24 (group II). Negative exercise tests were stated also in a group of 73 healthy subjects (control group-III). Tolerance of physical exercise, probability of coronary heart disease, rest and exercise arterial blood pressure values and left-ventricular systolic time intervals (LVSTI) were analysed in these groups. The preejection period (PEP) and PEP/LVET ratio increased and left-ventricular ejection time index (LVETI) decreased at rest in patients with the second period of PAH as compared in healthy subjects. It proved that left-ventricular mechanical function had been damaged. Submaximal physical exercise proceeded however with similar changes of LVSTI as healthy subjects. There were found high pretest probability of coronary heart disease, decreased tolerance of submaximal physical effort and decreased left-ventricular mechanical function in patients with positive exercise test. Rest values of PEPI and PEP/LVET ratio were significantly higher and LVETI were lower in I than in II (p less than 0.05) an in III group (p less than 0.001). Increased values of PEPI, LVETI and PEP/LVET ratio in relation to the second group and much more as compared in the control group were observed during physical effort.
 ...
PMID:[Dynamics of left ventricular systole in primary arterial hypertension with a positive submaximal stress test]. 294 26

A high frequency of immunological disturbances were recorded in 19 mild and 23 malignant hypertensive patients. IgG levels were raised in patients who survived a malignant phase of hypertension. We also found increased frequency of autoantibodies (26% vs. 9% in controls), increased T-lymphocyte reactivity against arterial-wall antigens (p = 0.001), a significant frequency of low responders to PHA (p = 0.003), and a statistically significant correlation (p = 0.031) between the presence of autoantibodies and T-cell hyper-reactivity against arterial antigens in mild hypertensive patients. We suggest that these abnormalities might be relevant in the pathogenesis of some hypertensive conditions. Autoantibody production is likely to be correlated with a predisposition to hypertension through some autoimmune mechanisms.
 ...
PMID:Humoral and cellular immunological abnormalities in hypertensive patients. 387 29

Spontaneously hypertensive male and female rats (SHR) were compared with Wistar/Kyoto (W/K) controls at 15 wk and 80 wk of age. Treatment of the young and old hypertensives with thymosin, fraction 5, lowered the blood pressure within 4 wk of the start of treatment. Following 10 wk of injections, the blood pressures of the hypertensive rats remained at a depressed level for about 6 wk. The thymic hormone raised the depressed spontaneous T-cell rosette formation of the aged hypertensive rat and increased the lymph node T-cell response to the mitogens, Con A and PHA. Thymosin administration over a period of 7 wk increased the size of the aged hypertensive thymus. No similar effect was observed in the W/K. Spleen cell production of prostaglandin E (PgE) was markedly higher in the young hypertensive and immune complex deposition was found in the glomeruli and tubules of the aged SHR kidneys. Thymosin lowered the high level of PgE to normal and decreased the immune complex deposition in the kidney. IgG1 levels were considerably depressed in the SHR as compared to the W/K. Following thymosin administration levels of IgG1 increased 2-fold in both rat strains. Plaque-forming cells from the spleens of the untreated SHR were about 3-fold less than those of the age-matched W/K. Following treatment with thymosin the number of plaque-forming cells of both groups demonstrated a substantial further decrease. Spontaneous hypertension in rats is similar, in certain respects to autoimmune-like diseases in humans with a depression in T-cell activity as well as immune complex deposition; both conditions being altered by exposure to a thymic extract.
 ...
PMID:Immune response modulation in the spontaneously hypertensive rat. 634 14

A strain of SHR which develops hypertension spontaneously is marked by a selective depression of T-cell functions associated with an early appearance of natural thymocytotoxic autoantibody and a deficiency of thymic hormone. Present results demonstrate that various immunopotentiators (IPs) such as thymostimulin (TS), PS-K, SPG, neurotropin (NSP), and K-247 partially or almost completely reversed the T-cell depression in these SHR as detected by a rosette forming test, plaque-forming assay and blastogenesic response to PHA and Con A. In contrast, these IPs had no effect on the immune responsiveness of WKA rats with normal T-cell functions. Among the IPs, NSP, which had an almost complete restorative effect on the T-cell functions of SHR, induced significant transplantation resistance to the syngeneic tumor challenge. A new synthetic product K-247 also induced a significant suppression of lethal tumor growth in SHR, though its restorative effect on T-cell functions was weak. The fact that K-247 had a suppressive effect on tumor cell growth in vitro indicates that biochemical modifications rather than immunological ones may be involved. However, none of the IPs induced antitumor resistance in normal WKA rats. These results suggest that this strain of SHR provides a useful animal model for evaluation of various IPs.
 ...
PMID:Screening of various immunopotentiators in spontaneously hypertensive rats with T-cell depression. 660 19

Cell-mediated immunity was investigated in spontaneously hypertensive rats (SHR). The thymuses of young SHR rats before developing hypertension had reduced numbers of immature T lymphocytes which were detected by the rosette formation test with guinea-pig erythrocytes in the presence of foetal bovine serum, whereas the thymuses of eight other rat strains tested contained about 60% of rosetting cells. The number of rosetting cells decreased progressively with age. The blastogenic responses to PHA and Con A of the SHR rats' lymphocytes was depressed to less than one-fifth when compared to those of othe rat strains including W/7k rats, the original colony of the SHR rats. Eight-month-old SHR rats showed fewer mitogenic responses than those of 2-month-old SHR rats. Other cell-mediated immune responses, including delayed hypersensitivity, allograft rejections, and a co-operation of T and B lymphocytes to produce humoral antibody formation were depressed significantly when compared to those of other rat strains. Possible mechanisms of immunological depression in the SHR rats in relation to the devleopment of hypertension are discussed.
 ...
PMID:Immunological depression in spontaneously hypertensive rats. 699 74

We have determined the effects of bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) on activity in the hypothalamo-pituitary-adrenal (HPA) system. Acutely, during the first 5 days, lesions of the anterior-medial VMH caused loss of the diurnal rhythms in food intake and plasma corticosterone (B) levels. Plasma B concentrations were elevated during the time of the normal trough of the basal diurnal rhythm in HPA axis activity and the diurnal rhythm in food intake was abolished, in agreement with the results of others. Consistent with hyperactivity in the HPA axis, lesioned rats had increased adrenal weight, decreased thymus and body weights and decreased plasma transcortin concentrations. To determine how lesions of the VMH provoke these increases in activity of the HPA system, the sensitivity of ACTH in adrenalectomized, lesioned rats to replacement with exogenous B was determined under basal conditions during the trough (morning-AM) and peak (evening-PM) of the diurnal rhythm in HPA axis activity. ACTH in lesioned rats in the AM was insensitive to feedback over the very low range of plasma B of 1-4 micrograms/dl, whereas sham-lesioned controls exhibited the normal, high sensitivity of ACTH to B at this time of day. There was no difference between the sensitivity of ACTH to this low range of B in the PM in VMH- and sham-lesioned rats. Two to 5 weeks after VMH lesions, as found by others, mean daily plasma B levels did not differ from sham-lesioned controls; however, plasma B during the AM was still mildly elevated in these rats. Inhibition of plasma B in the PM by dexamethasone was less effective in lesioned rats. Although HPA system responses to hypoglycemia, corticotropin-releasing factor and ACTH were normal, the lesioned rats exhibited obesity, hyperinsulinemia, hyperglycemia, hypertension and tachycardia, all signs consistent with mild hyperactivity of the PHA axis. Occupancy of type I, high-affinity corticosteroid receptors is known to control basal activity of the HPA system during the trough of the diurnal rhythm and to interact with glucocorticoid receptors to affect basal activity during the peak of the diurnal rhythm and during AM stress. We conclude that VMH lesions disrupt transmission of inhibitory signals, mediated by occupancy of type I corticosteroid receptors, that are initiated by a B feed-back site.
 ...
PMID:Ventromedial hypothalamic lesions inhibit corticosteroid feedback regulation of basal ACTH during the trough of the circadian rhythm. 778 59

The purpose of this study was to examine the roles of brain opioid receptors, using the opioid receptor antagonist naloxone, and brain alpha 2 adrenergic and imidazole receptors, using their agonist clonidine, in the hypertension and tachycardia induced by electrical stimulation of the AHA and PHA area. Unanesthetized and unrestrained Wistar rats 300-400 g that had previously had catheters inserted into the lateral cerebral ventricle and femoral artery and electrodes in AHA or PHA areas received intracerebral (ICV) administration of naloxone or clonidine prior to hypothalamic stimulation. AHA and PHA stimulation with current strength from 0.5 to 2.0 mA produced a significant (p < 0.05) and dose dependent increase in BP and heart rate. Naloxone reduced the increase in BP with AHA stimulation at all but the highest stimulation current intensity. Clonidine also blunted the BP increase to AHA stimulation but to a lesser degree than naloxone. The combination of both naloxone and clonidine completely prevented the increase in BP even at high current intensities. Both naloxone and clonidine prevented the increase in heart rate with AHA stimulation. In contrast to AHA stimulation, naloxone did not alter the BP increase produced by PHA stimulation while clonidine prevented the effects of PHA stimulation. Heart rate did not increase with PHA stimulation. These data suggest that (i) the mechanisms involved in the hypertensive response to AHA are different from that of PHA. (ii) the endogenous opioid system is more operative in mediating the BP elevation produced by AHA but not PHA stimulation (iii) activation of the central alpha adrenergic or imidazole receptors can suppress hypertensive response to both AHA and PHA but is more effective for PHA than AHA stimulation.
 ...
PMID:Comparative effects of central administration of naloxone and clonidine on the blood pressure and heart rate response to anterior and posterior hypothalamic stimulation. 817 7

Aspects of T and B cell function were studied in women with pregnancy-induced hypertension (PIH) and normotensive pregnant women by determining the proliferation of peripheral blood mononuclear cells (PBMC) with or without stimulation by mitogens (PHA, ConA and PWM) and by determining IgG and IgM levels in the culture supernatant. The results showed that the proliferation of PBMC without mitogens was significantly increased in PIH women without proteinuria compared with normotensive pregnant women. In the presence of PHA, [3H]thymidine uptake in PBMC was statistically higher in PIH women both with and without proteinuria than that in normotensive pregnant women. ConA and PWM mitogen activities were not significantly different between PIH women and normotensive pregnant women. Compared with normotensive pregnant women, IgG production was significantly increased in PIH women with proteinuria but not in those without proteinuria. IgM production was not changed in PIH women. We concluded that immunologic responses in PIH women were increased rather than decreased. This increased immunologic activity is in accordance with some important changes seen in PIH, such as an increase in intracellular calcium, the presence of blood-borne mitogenic factor and a decrease in prostaglandin E series. These findings also support the hypothesis that PIH might result from the imbalance between fetal antigenic load and maternal production of immunologic blockade.
 ...
PMID:Immunological changes in pregnancy-induced hypertension. 818 16

Pentoxifylline (PTX) has recently been shown to modulate TNF-alpha production and to reduce the incidence and severity of all major complications after BMT, including mucositis, veno-occlusive disease, renal insufficiency, hypertension, and graft-versus-host disease. To analyze in detail the effect of PTX on immune complications after BMT, we investigated the immunomodulatory effect of PTX on immune responses in vitro. The continuous presence of PTX significantly reduced the proliferative response of PBMC to PHA stimulation and to alloantigens in a dose-dependent manner. Starting at concentrations of 100 micrograms/ml, PTX was able to inhibit and, at 1000 micrograms/ml, completely block mitogen-induced proliferation. Maximal inhibition of more than 90% (91 +/- 4%) was also observed at PTX concentrations of 1000 micrograms/ml in the mixed lymphocyte culture (MLR) and by addition on day 0. However, lower but still significant suppression (13 +/- 7%) was achieved at concentrations of 10 micrograms/ml PTX. The inhibitory capacity of PTX was increased by mAbs against TNF-alpha (34 +/- 5% additional suppression at 100 micrograms/ml PTX) and not reversed by the addition of rTNF-alpha. The effect of PTX on the generation of CTLs in vitro was studied in the cell-mediated lymphotoxicity assay. PTX (100 micrograms/ml) significantly inhibited (P = 0.0178) the in vitro generation of CTLs when PTX was added to the culture on day 0. PTX also showed profound modulatory properties in the NK assay, with a reduction of 23 +/- 3% in specific lysis at 10 micrograms/ml PTX and maximal reductions of 88 +/- 3% at 1000 micrograms/ml PTX. Immunomodulatory properties of PTX were not only associated with blockage of TNF-alpha, as shown by decreased mRNA expression and TNF-alpha values in the culture supernatants, but also with an impaired production of other cytokines and secondary messages such as IFN-gamma and neopterin. PTX treatment, however, did not affect IFN-alpha or IL-1 beta production, and IL-6 release was even increased. PTX, therefore, has profound immunomodulatory properties in vitro, which are associated with selective inhibition of cytokine release and can be enhanced by the addition of mAbs against TNF-alpha, but not reversed by the addition of rTNF-alpha.
 ...
PMID:Immune response modulation by pentoxifylline in vitro. 833 42


1 2 3 4 Next >>