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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exercise training has reversible beneficial effects on cardiovascular diseases, e.g. hypertension, which may result from a decrease in systemic vascular resistance. The purpose of this study was to investigate possible mechanisms associated with the changes in vascular reactivity in large and small arteries with vasoconstrictors and vasodilators in rats after exercise. Wistar-Kyoto rats were trained for 8 weeks (Ex group) on a treadmill and compared with sedentary counterparts (Sed group). After the measurement of blood pressure and heart rate at 8 weeks, rat mesenteric arteries and thoracic aortas were excised and prepared as rings for this study. In addition, special care was taken not to damage the endothelium of the preparations. Our results showed that exercise training for 8 weeks (1) not only prevented an increase in blood pressure but also caused a fall in heart rate, (2) attenuated the contractions induced by both prostaglandin F(2alpha) (PGF(2alpha)) and high K(+) in the mesenteric artery, but reduced the PGF(2alpha)-induced contraction in the aorta only, (3) enhanced the relaxation elicited by acetylcholine (ACh) in both mesenteric arteries and aortas, and (4) increased nitrate [an indicator of nitric oxide (NO) formation] in plasma. The enhancement of ACh-induced relaxation in the mesenteric arteries in the Ex group was suppressed by pretreatment with N(omega) -nitro-L-arginine methyl ester (L-NAME), tetraethylammonium (TEA; a nonselective inhibitor of K(+) channels) or charybdotoxin [CTX; a selective inhibitor of large-conductance calcium-activated K(+) (BK(Ca)) channels], whereas in the aorta that response was attenuated by TEA or CTX and almost completely abolished by L-NAME. However, with a combination of L-NAME plus CTX in the mesenteric artery, ACh-induced relaxation was completely abolished in the Sed group, but not in the Ex group. These results suggest that in addition to NO, activation of BK(Ca) channels in the vascular beds, at least in part, also contributes to vasodilatation in animals with exercise training.
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PMID:Exercise training activates large-conductance calcium-activated K(+) channels and enhances nitric oxide production in rat mesenteric artery and thoracic aorta. 1138 96

For the treatment of different forms of systemic sclerosis (SSc), drugs play a predominant role. Depending on disease activity as well as type and severity of cutaneous, vascular and internal organ manifestations, different systemic (antiinflammatory, immunosuppressive, antifibrotic) or organ-specific therapies are used. The scientific basis of most treatment modalities is insufficient and incomplete. There is sufficient evidence for an antiinflammatory and antiproliferative efficacy of glucocorticosteroids, methotrexate, cyclophosphamide and cyclosporine A in the treatment of diffuse cutaneous systemic sclerosis. Vasoactive therapies play an important role in treating Raynaud's phenomenon (nifedipine or other dihydropyridines, prostaglandin analogs, losartan, prazosine), and arterial (ACE blockers, AT-1 antagonists) or pulmonary (epoprostenol) hypertension. Cyclophosphamide is effective in fibrosing alveolitis, prokinetic substances (metoclopramid, domperidone) in gastroesophageal dysmotility or octreotide in intestinal pseudoobstruction. Physical therapies (e.g., massage) are poorly studied. In particular cases, surgical measures (e.g., removal of calcifications) are necessary.
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PMID:[Evidence-based therapy of systemic sclerosis]. 1182 42

1. Ionic channels appear to play an important role in contractile responses of the cerebral arteries and, thereby, contribute to the regulation of cerebral circulation. In the present study, we investigated the role of large-conductance Ca(2+)-activated K+ (BK(Ca)) channels in the regulation of cerebral arterial tone during chronic hypertension. 2. Ring segments of the basilar artery from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were placed in bath chambers and the isometric tension of each ring was measured. 3. Application of inhibitors of BK(Ca) channels, namely tetraethylammonium (TEA; > or = 0.1 mmol/L) and charybdotoxin (CTX; > or = 0.1 nmol/L), produced spontaneous contraction with rhythmic oscillation in the basilar artery from SHR. 4. The oscillatory contraction was not induced by 5-hydroxytryptamine (0.01-10 micromol/L) or depolarization by external high K+ (20-60 mmol/L). 5. The rhythmic contraction was completely abolished by either the removal of external Ca(2+) or the application of nicardipine (10 nmol/L). 6. The oscillation was not affected by the substitution of external Cl(-) by various equimolar anions (i.e. acetate, benezenesulphonate, bromide and isethianate). 7. The amplitude of the oscillation was dose-dependently increased by the vasodilators forskolin and sodium nitroprusside, as well as by stimulation of the endothelium with histamine and acetylcholine, whereas the frequency was decreased. 8. In contrast, the oscillation was eliminated by depletion of Ca(2+) stores by caffeine. Neither TEA (10 mmol/L) nor CTX (10 nmol/L) produced any significant contraction of the basilar artery in WKY rats. 9. These results suggest that BK(Ca) channels may play an important role in regulating the resting tone of the cerebral artery in SHR.
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PMID:Role of CA(2+)-activated K+ channels in the regulation of basilar arterial tone in spontaneously hypertensive rats. 1206 Jan

The current recommendations of kidney biopsy in childhood idiopathic nephrotic syndrome (CINS) were put forward to minimize unnecessary kidney biopsies in underlying minimal change disease (MCD). However, there remains a diversity of opinion about the criteria for biopsying children with idiopathic nephrotic syndrome. This study was conducted to prospectively study their usefulness in avoiding biopsies in MCD and to evaluate further modifications for minimizing biopsies in CINS. Of 400 consecutive CINS patients, 222 patients were subjected to kidney biopsy according to the current recommendations. The histopathology spectrum of these selectively biopsied children revealed focal segmental glomerulosclerosis (FSGS) in 39%, MCD in 34.2%, membranoproliferative glomerulonephritis (MPGN) in 16.2%, mesangioproliferative glomerulonephritis (MesPGN) in 7.6%, membranous nephropathy (MN) in 1.8%, and diffuse mesangial sclerosis (DMS) in 0.9%. We observed that despite the current recommendations and efforts to minimize biopsy, 34% of children had MCD on histopathology. Two or more clinical (hematuria and hypertension) or biochemical (renal insufficiency) parameters were present in all children with MPGN. Low C3 was present only in children with MPGN. All the steroid responders were found to have MCD, FSGS, or MesPGN on biopsy. Cyclophosphamide response correlated better with steroid responsiveness ( P=0.02) than with histo- pathology ( P=0.80) in MCD, FSGS, and MesPGN. Based on these observations, we suggest some modifications in current recommendations for kidney biopsy to minimize biopsying children with MCD. These are (1) biopsies in children (age 1-16 years) should be restricted (a) to a subgroup with two or more clinical and biochemical parameters and (b) in steroid non-responders, (2) the decision to administer cyclophosphamide should be based on steroid response pattern without requiring a prior routine biopsy.
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PMID:Do current recommendations for kidney biopsy in nephrotic syndrome need modifications? 1210 3

Despite its widespread use, there are only a few published studies of the use of intravenous high-dose pulse cyclophosphamide in lupus nephritis in children. There are few data about the long-term efficacy and safety of this form of therapy. This study evaluates the clinical efficacy of this regimen in children with severe lupus nephritis followed prospectively over a 5-year period. Nine children with severe active lupus nephritis were enrolled in a treatment regimen of monthly intravenous pulses of cyclophosphamide (0.75-1 g/m(2)) for 6 months and then every 3 months for a total of 36 months. Cyclophosphamide treatment was associated with significant improvement in renal function during treatment. However, data presented here show that 56% of the patients progressed to chronic renal failure and 22% required dialysis 2 years after discontinuation of cyclophosphamide therapy. Hence it seems that this regimen is not effective in our patients in the long term, especially patients who present with high serum creatinine and hypertension.
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PMID:Cyclophosphamide therapy for lupus nephritis: poor renal survival in Arab children. 1270 Sep 62

Dietary strategies to prevent and treat osteoporosis focus on increased intake of calcium and vitamin D. Modification of whole dietary patterns and sodium reduction may also be effective. We examined the effects of two dietary patterns and three sodium levels on bone and calcium metabolism in a randomized feeding study. A total of 186 adults, aged 23-76 y, participated. After a 2-wk run-in period, participants were assigned randomly to diets containing three levels of sodium (50, 100 and 150 mmol/d) to be consumed for 30 d in random order. Serum osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), fasting serum parathyroid hormone (PTH), urinary sodium, potassium, calcium and cAMP were measured at baseline and at the end of each sodium period. The Dietary Approaches to Stop Hypertension (DASH) diet reduced serum OC by 8-11% and CTX by 16-18% (both P < 0.001). Urinary calcium excretion did not differ between subjects that consumed the DASH and control diets. Reducing sodium from the high to the low level significantly decreased serum OC 0.6 microg/L in subjects that consumed the DASH diet, fasting serum PTH 2.66 ng/L in control subjects and urinary calcium 0.5 mmol/24 h in both groups. There were no consistent effects of the diets or sodium levels on urinary cAMP. In conclusion, the DASH diet significantly reduced bone turnover, which if sustained may improve bone mineral status. A reduced sodium intake reduced calcium excretion in both diet groups and serum OC in the DASH group. The DASH diet and reduced sodium intake may have complementary, beneficial effects on bone health.
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PMID:The DASH diet and sodium reduction improve markers of bone turnover and calcium metabolism in adults. 1451 96

5-Hydroxytryptamine (5-HT) is a potent pulmonary vasoconstrictor and contributes to hypoxic pulmonary vasoconstriction and pulmonary arterial hypertension. Small intrapulmonary vessels are very sensitive to hypoxia and play a major role for blood flow regulation in the lung. Thus we have investigated the mechanisms involved in the calcium signal to 5-HT in rat small intrapulmonary artery (IPA). Effects of 5-HT were examined in isolated IPA (external diameter <250 microm) from rat. Digital imaging with fura-PE3 was used to record intracellular calcium concentration ([Ca(2+)](i)) and to follow external diameter of the vessels. 5-HT induced a sustained [Ca(2+)](i) variation that was sensitive to the inhibitor of the 5-HT(2A) receptors, ketanserin, and insensitive to voltage-dependent L-type calcium channel blockers (nitrendipine and nicardipine) or voltage-independent calcium channel antagonists (LOE-908, SKF-96365, and gadolinium). The calcium response to 5-HT was also not modified by a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor (cyclopiazonic acid; CPA), which depletes intracellular calcium stores. CPA alone activated a capacitative calcium channel that was sensitive to LOE-908 and insensitive to SKF-96365 and gadolinium. The sustained calcium signal to 5-HT was partly blocked by inhibitors of arachidonic acid production (RHC-80267 and isotetrandrine) and mimicked by application of exogenous arachidonic acid. These results suggest that activation of a noncapacitative, arachidonic acid-sensitive, receptor-operated calcium channel contributes to 5-HT-induced sustained calcium increase in small IPA.
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PMID:5-HT induces an arachidonic acid-sensitive calcium influx in rat small intrapulmonary artery. 1475 48

Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis and visceral disease. Therapy is organ and pathogenesis targeted. In this review, we describe novel strategies in the treatment of SSc. Utilizing the MEDLINE and the COCHRANE REGISTRY, we identified open trials, controlled trials, for treatment of SSc from 1999 to April 2005. We used the terms scleroderma, systemic sclerosis, Raynaud's phenomenon, pulmonary hypertension, methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, IVIg, calcium channel blockers, losartan, prazocin, iloprost, N-acetylcysteine, bosentan, cyclophosphamide, lung transplantation, ACE inhibitors, anti-thymocyte globulin, and stem cell transplantation. Anecdotal reports were omitted. Methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, and IVIg may be beneficial in improving the skin tightness in SSc. Calcium channel blockers, the angiotensin II receptor type 1 antagonist losartan, prazocin, the prostacyclin analogue iloprost, N-acetylcysteine and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. Epoprostenol and bosentan are approved for therapy of pulmonary hypertension (PAH). Other options under investigation include intravenous or aerolized iloprost. Cyclophosphamide (CYC) pulse therapy is effective in suppressing active alveolitis. Stem cell and lung transplantation is a viable option for carefully selected patients. Renal crisis can be effectively managed when hypertension is aggressively controlled with angiotensin converting enzyme (ACE) inhibitors. Patients should continue taking ACE inhibitors even after beginning dialysis in hope of discontinuing dialysis. Antithymocyte globulin and mycophenolate mofetil appear safe in SSc. The improvement in skin score and the apparent stability of systemic disease during the treatment period suggest that controlled studies of these agents are justified. Stem cell transplantation is under investigation for severe disease. Novel therapies are currently being tested in the treatment of SSc and have the potential of modifying the disease process and overall clinical outcome. The evaluation of these studies is still a difficult process.
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PMID:New therapeutic strategies for systemic sclerosis--a critical analysis of the literature. 1629 21

A 32-year-old Japanese woman, who had a treatment history of systemic lupus erythematosus (SLE) with lupus nephritis World Health Organization class IV for 11 months, visited our hospital due to fever, facial erythema, and erosion of the oral cavity on November 10, 2003. Her mucosal erosion and facial skin erythema progressed over the following week, and Stevens-Johnson syndrome was diagnosed due to pathological findings of the skin. Among the administrated drugs, only mizoribine, started 6 months earlier, produced a positive reaction in the drug lymphocyte stimulation test. Increased prednisolone and high dose intravenous gamma-globulin were given successfully. Cyclosporine at 50 mg was administered to control the SLE, followed by an increase to 100 mg on January 7, 2004. She suffered from abdominal pain, blindness, and convulsion on January 9. The magnetic resonance image of her brain prompted a diagnosis of reversible posterior leukoencephalopathy syndrome. After withdrawal of cyclosporine and control of hypertension, symptoms disappeared rapidly. Cyclophosphamide pulse therapy was successfully administrated to control lupus nephritis. This is the first report describing the relationship between Stevens-Johnson syndrome and mizoribine. Although the use of mizoribine is thought to be safe, careful observation is necessary.
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PMID:Stevens-Johnson syndrome induced by mizoribine in a patient with systemic lupus erythematosus. 1663 33

Systemic sclerosis (scleroderma) is considered as the most severe connective tissue disease. It is characterized by an abnormal immune activation, a vasculopathy and a fibrosis of the skin and of multiple internal organs. Numerous progress in the understanding of the pathogenesis with identification of key molecules have permit to introduce novel treatments that improve the management of some aspects of the disease. ACE inhibitors are effective in resolving renal crisis. Cyclophosphamide is useful for treatment of fibrosing alveolitis. Prostaglandins, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors permit to improve the treatment of the vascular complications (digital ulcerations, pulmonary arterial hypertension) of scleroderma.
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PMID:[Pathogenic mechanisms in systemic sclerosis and their therapeutical consequences. Part 2: treatment]. 1671 Nov 51


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