Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclosporine has dramatically improved the success rates for all forms of organ transplantation. However, its use is complicated by the frequent occurrence of hypertension and reversible nephrotoxicity. The iatrogenic hypertension induced by cyclosporine resembles a low-renin, salt-sensitive form of essential hypertension, which is often controlled with salt restriction and therapies counteracting renal salt acquisition, e.g., diuretics and calcium channel blockers (CCBs). CCBs may also counteract the direct vasoconstrictive effects of cyclosporine, as well as the effects of other vasoconstrictors, such as endothelin or thromboxane, that may be stimulated by cyclosporine. Additionally, CCBs may potentiate the immunosuppression of cyclosporine, yet minimize nephrotoxicity. We demonstrated that the in vitro combination of verapamil and cyclosporine had an additive inhibitory effect on the activation and function of human peripheral blood mononuclear cells in several assays of the afferent and efferent limbs of immunologic responses. This additive immunosuppression was not likely to have been related to these drugs' effects on interleukin-2 (IL-2) circuitry, since no additive inhibition of IL-2 production or IL-2 responsiveness was found. There was some additive inhibition of IL-2 receptor expression at the higher concentrations of verapamil and cyclosporine that were tested. Although the combination of verapamil and cyclosporine additively inhibited mitogen-induced 45Ca uptake, the inhibitory effect of cyclosporine appears to be due to an inhibition of lymphocyte activation rather than direct inhibition of calcium flux through the slow calcium channel, suggesting that the two drugs do not have additive effects in depressing the transmembrane flux of calcium. More recently, we have demonstrated that the inactive enantiomer of verapamil, which does not block the slow calcium channel, has identical immunosuppressive capabilities as the active enantiomer. Thus, the antiproliferative effect of verapamil is probably slow-calcium-channel independent and may represent the ability of the drug to interfere with muscarinic, alpha 1-adrenergic, or even opiate receptors on lymphocytes or to block lymphocyte potassium channels. An even better possibility is that verapamil may diminish necessary precursor molecule uptake into lymphocytes, since both the inactive and active isomeric forms of verapamil are capable of diminishing thymidine, uridine, and leucine incorporation into stimulated lymphocytes--necessary for DNA, RNA, and protein synthesis, respectively. These in vitro observations may have clinical applicability, as early studies demonstrate reduced rejection rates of cyclosporine-treated transplant patients receiving CCBs. Consequently, CCBs are important medications to be considered for use in cyclosporine-treated organ transplant recipients.
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PMID:Therapeutic benefits of calcium channel blockers in cyclosporine-treated organ transplant recipients: blood pressure control and immunosuppression. 203 18

Recent reports indicate that cyclooxygenase inhibitors such as aspirin may facilitate the release of interleukin-2 from thymic T cells. We have previously reported that aspirin has antihypertensive effects in the standard animal model of essential hypertension, the spontaneously hypertensive rat (SHR). Because the SHR has been reported to be deficient in T cells, it was of interest to determine whether the course of hypertension in this model could be altered by interleukin-2, the T cell growth factor. A single bolus of interleukin-2 (5,000 units/kg s.c.) prevented the increase of blood pressure in the young SHR and lowered pressure to normotensive levels in the well-established hypertensive adult SHR. In the latter, the effects of a single dose have been found to persist for at least 6 months with no toxic or untoward effects apparent. Blood pressure in Goldblatt, single-kidney wistar-kyoto rats, a model of renal hypertension, was not affected by interleukin-2.
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PMID:Antihypertensive effect of interleukin-2. 213 45

Serum levels of soluble interleukin-2 receptors (IL2R) and of beta 2-microglobulin (beta 2M) were studied with the immunoenzymatic technique in 38 patients with primary glomerulonephritis (GN), in 10 patients with essential hypertension (EH) and in 30 healthy subjects. IL2R correlated with beta 2M (p < 0.05). IL2R and beta 2M were higher in patients with GN (p < 0.003, p < 0.001, respectively) and in patients with EH (p < 0.003, p < 0.01, respectively) than in healthy subjects. IL2R and beta 2M correlated with serum creatinine, but not with proteinuria. Our data would suggest the existence of lymphocyte activation in patients with GN. Only speculations can be advanced with regard to the observed increase in these parameters in EH patients.
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PMID:Soluble interleukin-2 receptors and beta 2-microglobulin in patients with primary glomerulonephritis. 826 20

Immune system disturbances have been implicated in the pathogenesis of essential hypertension. The aim of this study was to determine the levels of the interleukin-1 beta and soluble interleukin-2 receptors in serum samples from 114 hypertensive patients before any drug therapy because there are no well-established data regarding these immunologic mediators in essential hypertension. We found increased levels of interleukin-1 beta in 59.6% of patients, while soluble interleukin-2 receptors were not detected. The interleukin-1 beta levels were significantly higher in patients than in healthy controls (P = 0.0001). We conclude that patients with essential hypertension have high levels of interleukin-1 beta but not indicators of cellular immune activation in their sera. Further studies are in progress in order to confirm, explain and assess the clinical utility of the above findings.
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PMID:Elevated interleukin-1 beta in the circulation of patients with essential hypertension before any drug therapy: a pilot study. 891 69

The dysfunction of the immune system has been implicated in the cause of essential hypertension (EH). On the other hand, interleukin- 1beta (IL-1beta) has strongly been involved in the pathogenesis of atheromatosis, whereas our preliminary experiments in serum samples from hypertensive patients before any drug therapy have shown the presence of high concentrations of IL-1beta and the absence of interleukin-2 (IL-2). The aim of this study was first to confirm our preliminary findings and second to investigate the possible interrelation(s) among the parameters studied, particularly between the immunologic markers and the blood pressure or the lipid parameters, because so far there are no data regarding the possible participation of IL-1beta in the cascade phenomena presented during the process of EH such as atherogenesis. Serum samples from 28 consecutive unselected patients with EH before any drug administration or after discontinuation of the antihypertensive therapy for at least 4 weeks, 31 normotensive patients with familial hypercholesterolemia (FH, disease control group), and 35 healthy individuals In a control group matched for age and sex were investigated for the presence of IL-1beta (commercial enzyme immunoassay), soluble IL-2 receptors (slL-2Rs, sandwich enzyme-linked immunosorbent assay set up in our laboratory), and some of the acute phase proteins by nephelometry. In addition, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A1 and B, and lipoprotein (a) were determined by standard methods. The data were analyzed by unpaired t test, Mann Whitney-U, chi-squared analysis after Yate's correction, analysis of variance, or Kruskal-Wallis where applicable. Correlation coefficient was calculated by simple regression analysis (r) or nonparametric Spearman correlation coefficient (rs). We found that (1) none of the patients had increased concentrations of sIL-2Rs, and (2) the IL-1beta levels significantly differed in the three groups (p = 0.0001). In more detail, the concentrations of IL-1beta were significantly higher in patients with EH compared with those in patients with FH (p < 0.0005) and the healthy control group (p = 0.0001). By contrast, the IL-1beta concentrations did not differ between patients with FH and the healthy control group. (3) Sixteen (57.1%) patients with EH and only 6 (19.4%) patients with FH (p < 0.01) had increased levels of IL-1beta, and (4) the IL-1beta was not correlated with the acute phase reactants or the lipid parameters in the groups studied. However, the group of patients with EH and increased IL-1beta levels had significantly higher mean concentrations of triglycerides (p < 0.05) and significantly lower mean concentrations of high-density lipoprotein cholesterol (p < 0.05) than those who had IL-1beta levels lower than the cutoff point. (5) The IL-1beta concentrations were positively though slightly correlated with the mean blood pressure only in the group of patients with EH (r = 0.38, p < 0.05). This study demonstrated the presence of high concentrations of IL-1beta and the absence of indicators of cellular immune activation in the systemic circulation of patients with EH, suggesting that this cytokine may be involved in the pathogenesis of EH. In addition, this study showed that the high levels of IL-1beta were associated with lipid indicators of atheromatosis only in the group of patients with EH. More studies are required in an attempt to address whether IL-1beta could have a pathogenetic importance in EH. Taking into account these findings, however, it can be suggested that the presence of high IL-1beta levels may be an additional and perhaps independent risk factor for atheromatosis in patients with EH.
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PMID:Increased serum levels of interleukin-1beta in the systemic circulation of patients with essential hypertension: additional risk factor for atherogenesis in hypertensive patients? 904 11

Moringa oleifera is a plant whose fruits, roots and leaves have been advocated for traditional medicinal uses. The physicochemical analysis shows that Moringa oleifera contains more dietary polyunsaturated fatty acids (PUFA) than saturated fatty acids (SFA). The consumption of an experimental diet enriched with Moringa oleifera extracts lowered blood pressure in spontaneously hypertensive rats (SHR), but not in normotensive Wistar-Kyoto (WKY) rats as compared to rats fed an unsupplemented control diet. Anti-CD3-stimulated T cell proliferation was diminished in both strains of rats fed the Moringa oleifera. The experimental diet lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats fed the control diet. Studies of platelets from patients with primary hypertension and from SHR support the notion that the concentration of intracellular free calcium [Ca(2+)](i) is modified in both clinical and experimental hypertension. We observed that the basal, [Ca(2+)](i) was lower in T cells of SHR than in those of WKY rats fed the control diet. Feeding the diet with Moringa oleifera extracts to WKY rats did not alter basal [Ca(2+)](i) in T cells but increased basal [Ca(2+)](i) in SHR. Our study clearly demonstrated that Moringa oleifera exerts antihypertensive effects by inhibiting the secretion of IL-2 and modulates T cell calcium signaling in hypertensive rats.
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PMID:Moringa oleifera-rich diet and T cell calcium signaling in spontaneously hypertensive rats. 2840 7