salicylates and Hypertension

Topics: Antihypertensive Agents; Blood Coagulation Disorders; Cardiovascular Diseases; Coumarins; Drug Interactions; Epilepsy; Heparin; Humans; Hypertension; Lidocaine; Mental Disorders; Pharmaceutical Preparations; Phenothiazines; Phenytoin; Procainamide; Salicylates

Calcium antagonists were found to be associated with an increased risk of gastrointestinal haemorrhage (GIH) in hypertensive patients over 67 years old (Pahor et al. Lancet 1996; 347 : 1061). This unexpected result led us to investigate this question using the French pharmacovigilance system database. We use the case/non case methodology (Moore et al. Br J Pharmacol 1997; 44 : 513) where cases and non cases were both identified from the spontaneous adverse drug reaction (ADR) reporting database. Cases were reports of the reaction of interest (i.e. GIH as recorded in the database). Non cases were all reports of reactions other than being studied. Exposure was considered as the presence in a report of the drug of interest (calcium antagonists), whether or not it was suspected of causing the reaction. We calculated Odds ratios (OR) as the ratio of the Odds of the association of reports of GIH with calcium antagonists in cases and in non cases. Calcium antagonists included in the present study were dihydropyridines, diltiazem, verapamil and bepridil. Salicylates and non steroidal antiinflammatory drugs were used as positive controls. Among the 112,792 ADRs recorded in the database between January 1985 and December 1996, 864 (0.8%) were GIH. There was no association between GIH and the exposure to calcium antagonists whatever the class of the drugs (OR = 1.2, 95% CI: [0.9; 1.6]. A subgroup analysis among the GIH reported in patients over 65 years old (470 GIH from 37,462 ADRs) also failed to find any association (OR = 0.7, 95% CI: [0.5-1.0%]). The present results failed to confirm the hypothesis of an association between GIH and use of calcium antagonists.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Calcium Channel Blockers; Gastrointestinal Hemorrhage; Humans; Hypertension; Pharmacoepidemiology; Risk Factors; Salicylates

Although cyclosporine has been found to be effective therapy for severe psoriasis, only limited data exist about efficacy and safety during long-term treatment with a low-dose regimen. Furthermore, little is known about the course of psoriasis after drug withdrawal.. Our purpose was to assess the results of long-term therapy with cyclosporine for severe psoriasis with particular regard to efficacy and safety, as well as the disease course after stopping treatment.. A multicenter study of 217 patients treated with 1.25, 2.5, or 5.0 mg/kg per day of cyclosporine was performed. Duration of treatment ranged from 6 to 30 months followed by a posttreatment period of 3 months. Efficacy was assessed by the Psoriasis Area and Severity Index and safety was monitored by clinical and laboratory investigations.. Patients with severe psoriasis showing a reduction in the Psoriasis Area and Severity Index of 75% with their individual dose of cyclosporine maintained clinical improvement during continuous maintenance therapy. Newly occurring side effects were less frequent during the maintenance phase than in the induction phase. After withdrawal of cyclosporine, worsening of psoriasis requiring antipsoriatic therapy was seen in about half of the patients.. Cyclosporine is effective for long-term therapy for severe psoriasis and does not lead to severe deterioration of the disease after drug withdrawal.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Creatinine; Cyclosporine; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Ointments; Psoriasis; Recurrence; Safety; Salicylates; Salicylic Acid; Time Factors; Triglycerides

To evaluate whether imidazole salicylate, a recently developed NSAID, can interfere with the antihypertensive effect of atenolol and to compare its action with that of indomethacin, 9 essential hypertensives, while on prolonged (more than 1 month) treatment with atenolol (100 mg qd) received, according to a double-blind cross-over study, imidazole salicylate (750 mg t.i.d.) or indomethacin (50 mg b.i.d. plus a placebo tablet) for 1 week, reverting the treatment after a 2-week wash-out period. While indomethacin addition significantly increased blood pressure, when compared to atenolol alone, imidazole salicylate did not change it. These data show that imidazole salicylate, unlike indomethacin, does not reduce the antihypertensive effect of atenolol.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Atenolol; Blood Pressure; Drug Interactions; Evaluation Studies as Topic; Female; Humans; Hypertension; Imidazoles; Indomethacin; Male; Middle Aged; Random Allocation; Salicylates

Topics: Adult; Analgesics; Clinical Trials as Topic; Female; Humans; Hypertension; Kidney Failure, Chronic; Longitudinal Studies; Middle Aged; Phenacetin; Salicylates; Smoking; Substance-Related Disorders; Switzerland; Urinary Tract Infections

Chronic low-grade inflammation plays an important role in the pathogenesis of insulin resistance. In the current study, we tested the effects of salsalate, a non-steroidal anti-inflammatory drug, in an animal model of inflammation and metabolic syndrome using spontaneously hypertensive rats (SHR) that transgenically express human C-reactive protein (SHR-CRP rats). We treated 15-month-old male transgenic SHR-CRP rats and nontransgenic SHR with salsalate (200 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP and SHR rats were fed a standard diet without salsalate. In the SHR-CRP transgenic strain, salsalate treatment decreased circulating concentrations of the inflammatory markers TNF-α and MCP-1, reduced oxidative stress in the liver and kidney, increased sensitivity of skeletal muscles to insulin action and improved tolerance to glucose. In SHR controls with no CRP-induced inflammation, salsalate treatment reduced body weight, decreased concentrations of serum free fatty acids and total and HDL cholesterol and increased palmitate oxidation and incorporation in brown adipose tissue. Salsalate regulated inflammation by affecting the expression of genes from MAPK signalling and NOD-like receptor signalling pathways and lipid metabolism by affecting hepatic expression of genes that favour lipid oxidation from PPAR-α signalling pathways. These findings suggest that salsalate has metabolic effects beyond suppressing inflammation.

Topics: Adipose Tissue, Brown; Animals; Animals, Genetically Modified; C-Reactive Protein; Fatty Acids, Nonesterified; Humans; Hypertension; Inflammation; Insulin Resistance; Lipid Metabolism; Liver; Metabolic Syndrome; NLR Proteins; Oxidative Stress; PPAR alpha; Rats; Salicylates; Tumor Necrosis Factor-alpha

Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications. The purpose of this study was to examine the novel coumarin-aspirin compound XLF-III-43 in the inhibition of AGE formation in diabetic nephropathy. In vitro analysis showed XLF-III-43 in a dose-dependent manner decreased glucose induced formation of glycation adducts on albumin and inhibited AGE-lysozyme crosslinking. The streptozotocin-induced diabetic rats were used to investigate the beneficial effects of XLF-III-43 treatment on diabetic nephropathy. Administration of XLF-III-43 significantly decreased (P<0.05) blood urea nitrogen and urinary albumin excretion. Moreover, XLF-III-43 ameliorated kidney hypertrophy, mesangial expansion and glomerulosclerosis in diabetic rats relative to untreated model group. These data correlated with decreased both AGE and downstream markers of AGE stress (TGF-beta1, CTGF, fibronectin and collagen IV fibrolysis) in kidneys of diabetic rats. These data support further development of XLF-III-43 for prevention of nephropathy via inhibition of AGE formation consequent to chronic hyperglycemia.

Topics: Animals; Body Weight; Coumarins; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Female; Gene Expression Regulation; Glycation End Products, Advanced; Hyperglycemia; Hypertension; Kidney; Rats; Rats, Sprague-Dawley; Salicylates

We investigated N-adamantyl-N'-phenyl urea derivatives as simple sEH inhibitors. Salicylate ester derivatives have high inhibitory activities against human sEH, while the free benzoic acids are less active. The methyl salicylate derivative is a potent sEH inhibitor, which also has high metabolic and chemical stabilities; suggesting that such inhibitors are potential lead molecule for bioactive compounds acting in vivo.

Topics: Anti-Inflammatory Agents; Benzoates; Chemistry, Pharmaceutical; Drug Design; Epoxide Hydrolases; Humans; Hydrogen Bonding; Hydrolysis; Hypertension; Inhibitory Concentration 50; Kinetics; Models, Chemical; Salicylates; Spectrometry, Fluorescence; Urea

Compared with other non-steroid anti-inflammatory drugs (NSAIDs), aspirin is not correlated to hypertension. It has been shown that aspirin has unique vasodilator action in vivo, offering an explanation for the unique blood pressure effect of aspirin. In the present study, we investigate the mechanism whereby salicylates (aspirin and sodium salicylate) dilate blood vessels.. Rat aortic or mesenteric arterial rings were used to test the vascular effect of salicylates and other NSAIDs. RhoA translocation and the phosphorylation of MYPT1, the regulatory subunit of myosin light chain phosphatase, were measured by western blot, as evidenced for RhoA/Rho-kinase activation. Salicylates, but not other NSAIDs, relaxed contraction induced by most tested constrictors except for calyculin A, indicating that RhoA/Rho-kinase-mediated calcium sensitization is involved. The involvement of RhoA/Rho kinase in vasodilation by salicylates was confirmed by measurements of RhoA translocation and MYPT1 phosphorylation. The calculated half maximal inhibitory concentration (IC(50)) of vasodilation was apparently higher than that of cyclooxygenase inhibition, but comparable to that of proline-rich tyrosine kinase 2 (PYK2) inhibition. Over-expression of PYK2 induced RhoA translocation and MYPT1 phosphorylation, and these effects were markedly inhibited by sodium salicylate treatment. Consistent with the ex vitro vascular effects, sodium salicylate acutely decreased blood pressure in spontaneous hypertensive rats but not in Wistar Kyoto rats.. Salicylates dilate blood vessels through inhibiting PYK2-mediated RhoA/Rho-kinase activation and thus lower blood pressure.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aorta, Thoracic; Aspirin; Blood Pressure; Blood Vessels; Cells, Cultured; Disease Models, Animal; Focal Adhesion Kinase 2; Hypertension; Male; Muscle, Smooth, Vascular; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; rho-Associated Kinases; rhoA GTP-Binding Protein; Salicylates; Signal Transduction; Vasoconstriction; Vasodilation

In the spontaneously hypertensive rat (SHR) and aging Wistar-Kyoto rats (WKY), acetylcholine releases an endothelium-derived contracting factor (EDCF) produced by endothelial cyclooxygenase-1, which stimulates thromboxane A2 receptors (TP receptors) on vascular smooth muscle. The purpose of the present study was to identify this EDCF by measuring changes in isometric tension and the release of various prostaglandins by acetylcholine. In isolated aortic rings of SHR, U 46619, prostaglandin (PG) H2, PGF2alpha, PGE2, PGD2, prostacyclin (PGI2) and 8-isoprostane, all activate TP receptors of the vascular smooth muscle to produce a contraction (U 46619>>8-isoprostane=PGF2alpha=PGH2>PGE2=PGD2>PGI2). The contractions produced by PGH2 and PGI2 were fast and transient, mimicking endothelium-dependent contractions. PGI2 did not relax isolated aortic rings of WKY and SHR. Acetylcholine evoked the endothelium-dependent release of thromboxane A2, PGF2alpha, PGE2, PGI2 and most likely PGH2 (PGI2>>PGF2alpha>or=PGE2>TXA2>8-isoprostane, PGD2). Dazoxiben abolished the production of thromboxane A2, but did not influence the endothelium-dependent contractions to acetylcholine. The release of PGI2 was significantly larger in the aorta of SHR than in WKY, and the former was more sensitive to the contractile effect of PGI2 than the latter. The inhibition of PGI-synthase was associated with an increase in PGH2 spillover and the enhancement of acetylcholine-induced endothelium-dependent contractions. Thus, in the aorta of SHR and aging WKY, the endothelium-dependent contractions elicited by acetylcholine most likely involve the release of PGI2 with a concomitant contribution of PGH2.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Animals; Aorta, Thoracic; Cyclooxygenase Inhibitors; Endothelium, Vascular; Enzyme Inhibitors; Hypertension; Imidazoles; In Vitro Techniques; Indomethacin; Nitrobenzenes; Prostaglandins; Prostaglandins I; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Salicylates; Sulfonamides; Thromboxane A2; Vasoconstriction; Vasoconstrictor Agents

Topics: Diabetes Mellitus, Type 2; Diagnosis, Differential; Drug Eruptions; Eczema; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Myocardial Infarction; Patch Tests; Platelet Aggregation Inhibitors; Salicylates

We reported previously that endothelium-intact superior mesenteric arteries (SMA) from N(omega)-nitro-L-arginine (L-NNA)-treated hypertensive rats (LHR) contract more to norepinephrine (NE) than SMA from control rats. Others have shown that nitric oxide (NO) synthase (NOS) inhibition increases cyclooxygenase (COX) function and expression. We hypothesized that augmented vascular sensitivity to NE in LHR arteries is caused by decreased NOS-induced dilation and increased COX product-induced constriction. We observed that the EC50 for NE is lower in LHR SMA compared with control SMA (control -6.37 +/- 0.04, LHR -7.89 +/- 0.09 log mol/l; P <0.05). Endothelium removal lowered the EC50 (control -7.95 +/- 0.11, LHR -8.44 +/- 0.13 log mol/l; P <0.05) and increased maximum tension in control (control 1,036 +/- 38 vs. 893 +/- 21 mg; P <0.05) but not LHR (928 +/- 30 vs. 1,066 +/- 31 mg) SMA. Thus augmented NE sensitivity in LHR SMA depends largely on decreased endothelial dilation. NOS inhibition (L-NNA, 10(-4) mol/l) increased maximum tension and EC50 in control arteries but not in LHR arteries. In contrast, COX inhibition decreased maximum tension in control arteries, suggesting that COX products augment contraction. Indomethacin did not affect NE-induced contraction in L-NNA-treated or denuded arteries. In control SMA loaded with the fluorescent NO indicator 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, indomethacin increased and L-NNA decreased NO release. Therefore, COX products appear to inhibit NO production to augment NE-induced contraction. With chronic NOS inhibition, this modulating influence is greatly diminished. Thus, in NOS-inhibition hypertension, decreased activity of both COX and NOS pathways profoundly disrupts endothelial modulation of contraction.

Topics: Adrenergic alpha-Agonists; Animals; Blotting, Western; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Endothelium, Vascular; Enzyme Inhibitors; Hypertension; Isoenzymes; Male; Membrane Proteins; Mesenteric Arteries; Muscle, Smooth, Vascular; Nitric Oxide Synthase; Nitroarginine; Nitrobenzenes; Norepinephrine; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Salicylates; Sulfonamides; Vasoconstriction

To report a case of increased blood pressure associated with the use of salsalate in an elderly patient with no prior history of hypertension.. A 78-year-old white man with no prior history of hypertension initiated salsalate therapy for low-back pain. Over the 15 months prior to the initiation of salsalate, his blood pressure averaged 127 +/- 7 mm Hg systolic and 84 +/- 6 mm Hg diastolic (mean +/- SD). After initiation of salsalate, he experienced significant elevations in blood pressure, which led to a preliminary diagnosis of hypertension. Blood pressure after initiation of salsalate averaged 150 +/- 13 mm Hg systolic and 95 +/- 5 mm Hg diastolic. No changes in medications or medication doses (with the exception of warfarin) occurred in the 18 months prior to or during salsalate therapy. His weight remained stable. A detailed review of his medical records and history revealed no other causes for these elevations in blood pressure. Salsalate therapy was discontinued and his blood pressure returned to normotensive levels (119 +/- 2 mm Hg systolic and 81 +/- 2 mm Hg diastolic).. Nonsteroidal antiinflammatory drug (NSAID)-induced elevations in blood pressure have been well documented in patients receiving antihypertensive medications. Due to its relative weak inhibition of cyclooxygenase and lack of published literature in hypertensive patients, salsalate is considered to have little or no effect on blood pressure. Our report documents a possible case of salsalate-induced hypertension in a previously normotensive elderly man. Observational studies suggest that NSAID use may increase the risk of developing hypertension in older patients.. Clinicians should be aware of the possible effects of NSAIDs on blood pressure. Blood pressure monitoring following the initiation of salsalate may be warranted, particularly in older patients.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Humans; Hypertension; Low Back Pain; Male; Salicylates

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Captopril; Female; Humans; Hypertension; Imidazoles; Indomethacin; Male; Middle Aged; Salicylates; Time Factors

Proteinuria may be the initial manifestation of serious renal disease or merely a laboratory finding of little clinical importance. Excretion of urinary protein in excess of 150 mg per 24 hours in an adult is abnormal. It may be of glomerular, tubular or overflow origin. A comparison of the dipstick and sulfosalicylic acid techniques helps distinguish the source of protein, and electrophoresis is confirmatory. Transient and intermittent proteinuria are not clinically important. Persistent proteinuria requires further investigation.

Topics: Benzenesulfonates; Child; Edema; Electrophoresis; Humans; Hypertension; Kidney Diseases; Methods; Proteinuria; Salicylates; Urinary Tract Infections; Urine

Keeping in mind the vasodilator action of prostaglandins, the control that they exercise over the vascular supply of kidneys and the sympathetic activity, research was conducted in order to establish the effect of arachidonic acid, the precursor of PGE2, on experimental hypertension in the rat. The experimental hypertension was induced by unilateral nephrectomy, followed by the administration of DOCA and the elevated sodium diet. The treatment was short in one group, long in the other, and both groups were compared to a control hypertensive group which received no treatment at all. Arachidonic acid worsened the experimental hypertension by 37% in the long treatment, and by 25% in the short treatment. The administration of lysine-acetylsalicylate diminished this hypertension. A non-saturated acid, oleic acid, which is not involved in prostaglandin synthesis, has no action. The authors would like to emphasize that in one of the previous experiments, L-tyrosine, the precursor of catecholamines, diminished the experimental hypertension in the rat, and also that L-DOPA and IMAO (MAOI) have comparable effects. It seems, therefore, that the depression of the central catecholaminergic activity, which is supposed to be the action of arachidonic acid via an increase in the PGE2 synthesis, appears to increase hypertension. It is noteworthy that the medial forebrain bundle (MFB) is catecholaminergic and that the periventricular system (PVS) is cholinergic. Thus hypertension may represent the peripheral vascular response to anguish which results from the activation of PVS and from the depression of MFB.

Topics: Administration, Oral; Animals; Arachidonic Acids; Blood Pressure; Hypertension; Kidney; Male; Nephrectomy; Rats; Salicylates; Time Factors

Topics: Acetaminophen; Antioxidants; Arachidonic Acids; Aspirin; Blood Platelets; Dronabinol; Fatty Acids; Hypertension; Indomethacin; Kinetics; Metals; Microsomes; Mixed Function Oxygenases; Oxidoreductases; Prostaglandin Antagonists; Prostaglandins; Salicylates; Species Specificity; Structure-Activity Relationship; Subcellular Fractions; Terminology as Topic; Time Factors

Topics: Anemia; Animals; Cattle; Dihydroxyphenylalanine; Dogs; Down Syndrome; Fever; Glycine; Humans; Hypertension; Liver Diseases; Methyldopa; Mitochondria, Liver; Pheochromocytoma; Rats; Salicylates; Swine; Uremia; Wounds and Injuries

Topics: Boric Acids; Diabetic Angiopathies; Female; Humans; Hypertension; Joint Diseases; Leg Ulcer; Male; Ointments; Salicylates; Varicose Ulcer; Zinc

Topics: Diuretics; Gout; Humans; Hypertension; Hypothyroidism; Kidney Diseases; Nicotinic Acids; Nucleoproteins; Proteins; Purines; Salicylates; Thioridazine; Uric Acid

Topics: Adult; Age Factors; Aged; Antihypertensive Agents; Blood Chemical Analysis; Blood Circulation; Blood Pressure Determination; Diuretics; Electrocardiography; Electrophoresis; Female; Humans; Hypertension; Male; Middle Aged; Natriuresis; Oscillometry; Plethysmography; Salicylates; Sulfonamides; Time Factors; Uric Acid

Topics: Animals; Anti-Inflammatory Agents; Bradykinin; Carbon; Female; Hypertension; Indomethacin; Phenylbutazone; Rats; Salicylates; Serotonin; Veins

Topics: Acidosis; Acute Kidney Injury; Alcoholism; Anuria; Child; Diabetes Mellitus; Dialysis; Humans; Hypertension; Hypertension, Malignant; Hyponatremia; Malaria; Peritoneal Dialysis; Poisoning; Renal Dialysis; Renal Insufficiency; Salicylates; Uremia

Topics: Hypertension; Iodides; Iodine; Iodine Compounds; Organic Chemicals; Phenobarbital; Reserpine; Salicylates; Theophylline