The release of the substrate for xanthine oxidase in hypertensive patients was suppressed by angiotensin converting enzyme inhibitors and α1-blockers

Ohtahara, Akira; Hisatome, Ichiro; Yamamoto, Yorihiro; Furuse, Masahiro; Sonoyama, Kazuhiko; Furuse, Yoshiyuki; Hamada, Toshihiro; Katoh, Masahito; Watanabe, Masashi; Kinugawa, Toru; Oginö, Kazuhíde; Igawa, Osamu; Shimomura, Tokio; Murakami, Fumiyo; Yamamoto, Tetsuya; Shigemasa, Chiaki

doi:10.1097/00004872-200103001-00009

Cited by 24 publications

(26 citation statements)

References 41 publications

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“…Small sample size may have contributed to the lack of statistical significance of some of the results, and did not allow us to perform multivariate analysis to detect factors responsible for the excess purine degradation. Second, number of control subjects was also small, but we would like to point out that control values for metabolites in this study were similar to those reported in our previous studies (9,13). Third, we acknowledge that the absence of clearance data for the metabolite is a limitation.…”

Section: Discussionmentioning

confidence: 50%

“…These findings suggest that HXis a good index of purine degradation through the purine nucleotide cycle, because the increased AMP deamination via activation of AMPdeaminase could accelerate the subsequent breakdown of inosine monophosphate to inosine, thereby leading to the increased formation of HX and Amm (1). Previous studies from our laboratory (9,13) showed that both HXand Ammlevels after forearm test increase in parallel. Thus, the augmented response in plasma HXto semi-handgrip exercise with the elevation of plasma Ammin the diabetic patients would reflect the activation of the purine nucleotide cycle in the exercising muscle.…”

Section: Discussionmentioning

confidence: 67%

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Excessive Purine Degradation druing Semi-ischemic Forearm Test in Patients with Diabetes Mellitus

Tanaka¹,

Hisatome

Kinugawa

et al. 2003

Intern. Med.

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Objective The aim of this study was to investigate whether or not the purine degradation in the skeletal muscle during forearm exercise is augmentedin patients with diabetes mellitus (DM).Methods Weused the semi-ischemic forearm test to examine the release of lactate (ALAC), ammonia (AAmm) and hypoxanthine (AHX) before exercise, 0, 4, 10, and 60 minutes after exercise in eleven diabetic patients and seven normal controls. ResultsThe sum of the increased HX (DM vs Controls: 26.1±21.2 vs 7.8±5.9 umol//, p<0.05) was greater in diabetic patients. Whenpatients were divided into the excessive response group (n=7) and normal response group (n=4), the maximumincrements in AHXand A Amm in the excessive response group (16.8±3.2 umol// and 122±60 umol//) were greater (p<0.05) than those in the control group (3.6± 3.0 umol// and 32±34 umol//) and the normal response group (2.9±2.9 umol// and 27.4±12.7 umol//). ALACboth in the excessive response group (5.4±1.5 mmol//) and the normal response group (3.6±1.0 mmol//) were higher (p<0.05) than that of the control group (1.7±0.5 mmol//). The prevalence of diabetic retinopathy was higher in the excessive response group than in the normal response group (75% vs. 25%). Conclusion These data suggest that patients with DM, especially with microangiopathy have augmented purine degradation during the semi-ischemic forearm test. Factors responsible for the augmented purine degradation in these patients remain to be determined. (Internal Medicine 42: 788-792, 2003)

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 67%

Excessive Purine Degradation druing Semi-ischemic Forearm Test in Patients with Diabetes Mellitus

Tanaka¹,

Hisatome

Kinugawa

et al. 2003

Intern. Med.

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“…Sur: serum uric acid, Uur: urinary uric acid, Scr: serum creatinine, Ucr: urinary creatinine, Uur/Ucr: urinary uric acid to urinary creatinine ratio, Cur/Ccr: urate clearance to creatinine clearance ratio, ARB angiotensin receptor blocker Irbesartan decreased Sur in both the group of patients where irbesartan was their fi rst angiotensin receptor blocker prescribed (fi rst group) and in the group of patients who were switched from another ARB (switch group), but did not affect Scr, Uur/Ucr, or Cur/Ucr in either group. genic hyperuricemia was caused by excessive degradation of the uric acid precursor hypoxanthine in skeletal muscles of hypertensive patients 7) . Losartan, one of the ARBs, has been reported to decrease Sur in hypertensive patients via inhibition of URAT1 20) , and several reports have shown that this property of losartan was abolished in hypertensive patients who carried a loss-offunction mutation in the URAT1 gene 21) .…”

Section: Discussionmentioning

confidence: 99%

“…The Guidelines for the Management of Hyperuricemia and Gout recommend the use of antihypertensive drugs that have favorable effects on uric acid metabolism, such as long-acting calcium channel blockers (CCBs), α-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), such as losartan 6) . CCBs, ACEIs, and α-blockers have been reported to suppress the production of the uric acid precursor hypoxanthine in skeletal muscles 7) . Losartan, specifically, has been reported to decrease Sur by enhancing urinary excretion of uric acid via inhibition of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) 8) .…”

Section: Introductionmentioning

confidence: 99%

Effects of Irbesartan on Uric Acid Metabolism in Patients with Treated Essential Hypertension

Miyazaki¹,

Sakuragi

Hamada

et al. 2018

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Abstract:Background: Irbesartan has been reported to inhibit renal uric acid reabsorption and thereby decrease serum uric acid (Sur) levels. However, its effect on uric acid metabolism in hypertensive patients has not been reported. Methods and Results: We conducted a retrospective observational study that included 40 hypertensive patients to clarify the effects of irbesartan (mean dose 87.5 mg) on blood pressure (BP) and uric acid metabolism [Sur, urinary uric acid (Uur), serum creatinine (Scr), urinary creatinine (Ucr), uric acid clearance (Cur), creatinine clearance (Ccr), urinary uric acid to urinary creatinine ratio (Uur/Ucr), and uric acid clearance to creatinine clearance ratio (Cur/Ccr)] at baseline and after 3 months of treatment. We allocated patients into two groups, patients with Uur/Ucr <0.5 (low Uur/Ucr group) or those with Uur/Ucr ! 0.5 (normal/ high Uur/Ucr group), into other two groups, patients with Cur/Ccr <5.5% (low Cur/Ccr group) or those with Cur/Ccr ! 5.5% (normal/ high Cur/Ccr group). The hypoexcretion group contained low Uur/Ucr group and low Cur/Ccr group, and the normal/ hyperexcretion group contained normal/high Uur/Ucr group and normal/ high Cur/Ccr group. Further, we allocated patients into another two groups, patients with Sur ! 7 mg/dl (hyperuricemic group) or those with Sur <7 mg/dl (normouricemic group). Irbesartan significantly decreased systolic BP without affecting heart rate, and decreased Sur without altering Uur/Ucr or Cur/Ccr. In the hypoexcretion group, irbesartan decreased Sur while increasing Uur/Ucr and Cur/Ccr. In contrast, in the normal/hyperexcretion and hyperuricemic groups, irbesartan decreased Sur without changing Uur/Ucr or Cur/ Ccr. In a normouricemic group, patients showed no changes in Sur after treatment with irbesartan. Conclusions: Irbesartan improved the secretion of uric acid, and reduced Sur in the hypoexcretion group, but did not influence uric acid excretion in the normal/hyperexcretion group. In hyperuricemic patients, irbesartan did not affect uric acid excretion but may have influenced uric acid production.

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“…In these patients, an excess of hypoxantine, which is produced in the muscle during exercise, 2,39 has been suggested to be converted to urate by the enzyme xantine oxidase. 40 The enzyme catalyses, in a single reaction, not only the synthesis of urate, but also that of the superoxide radical. As a matter of fact, recent evidence suggests that hypertensive patients exhibit in plasma a significantly higher production of this free radical than control subjects.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the antioxidant response in the plasma of healthy or hypertensive subjects after short-term exercise

Santangelo¹,

Cigliano

Montefusco³

et al. 2003

J Hum Hypertens

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Reactive oxygen species are produced during exercise. The antioxidants prevent or limit tissue damages by these species in physiological conditions. In particular, ascorbate and urate scavenge peroxynitrite, which can alter the function of many molecules, including the lecithin-cholesterol acyltransferase (LCAT) enzyme involved in reverse cholesterol transport. The aims of the present study were to compare the plasma antioxidant response to an ergometric test (ET) in hypertensive and healthy subjects, evaluate the exercise-dependent nitrosative stress in plasma, and assess whether the LCAT activity is altered by the exercise. Plasma samples, prepared before and after ET from hypertensive or healthy volunteers, were analysed for their levels of ascorbate, urate, a-tocopherol, retinol, nitrotyrosine, and LCAT activity. The a-tocopherol and retinol levels did not significantly change in both groups during exercise, while the ascorbate level changed displaying higher increase in controls (+38.8%) than in hypertensives (+17.2%). In these patients, during ET, the urate and nitrotyrosine levels changed more than in normotensives (+13.5 and +40.6% vs À3.1 and +25.2%, respectively). The antioxidants effectively prevented loss or reduction of LCAT activity, as it was similar in hypertensives and normotensives, and did not change after ET. The results demonstrate that exercise is associated with enhanced protein nitrosation, and suggest that the ascorbate or urate levels increase to limit oxidative damage.

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The release of the substrate for xanthine oxidase in hypertensive patients was suppressed by angiotensin converting enzyme inhibitors and α1-blockers

Cited by 24 publications

References 41 publications

Excessive Purine Degradation druing Semi-ischemic Forearm Test in Patients with Diabetes Mellitus

Excessive Purine Degradation druing Semi-ischemic Forearm Test in Patients with Diabetes Mellitus

Effects of Irbesartan on Uric Acid Metabolism in Patients with Treated Essential Hypertension

Evaluation of the antioxidant response in the plasma of healthy or hypertensive subjects after short-term exercise

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