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Background: Hypertension is a common complication in patients with gout and/or hyperuricemia. Besides, hyperuricemia is a risk factor of gout as well as ischemic heart disease in hypertensive patients. Moreover, the risk of gout is modified by antihypertensive drugs. However, it remains unclear how antihypertensive agents affect uric acid metabolism. Purpose: In the present study, we investigated the uric acid metabolism in treated hypertensive patients to find out whether any of them would influence serum levels of uric acid. Patients and methods: 751 hypertensive patients (313 men and 438 women) under antihypertensive treatment were selected. Blood pressure (BP), serum uric acid (SUA) and serum creatinine (Scr) were measured and evaluated statistically. Results: In patients treated with diuretics, beta-blockers and/or alpha-1 blockers SUA levels were significantly higher than in patients who were not taking these drugs. Besides, the estimated glomerular filtration rate (eGFR) in patients treated with diuretics, beta-blockers and/or alpha-1 blockers was negatively correlated with SUA level. There were gender differences in the effects of beta-blockers and alpha-1 blockers. Multiple regression analysis indicated that both diuretics and beta-blockers significantly contributed to hyperuricemia in patients with medication for hypertension. Conclusion: Diuretics, beta-blockers and alpha-1 blockers reduced glomerular filtration rate and raised SUA levels. Calcium channel blockers, ACE inhibitors and angiotensin receptor blockers, including losartan, did not increase SUA levels., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Although urate impaired the endothelial function, its underlying mechanism remains unknown. We hypothesized that urate impaired nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) via activation of uric acid transporters (UATs)., Purpose and Method: In the present study, we studied effects of urate on NO production and eNOS protein expression in HUVEC cells in the presence and absence of urate lowering agents using molecular biological and biochemical assays., Results: HUVECs expressed the 4 kinds of UATs, URATv1, ABCG2, MRP4 and MCT9. Exposure to urate at 7 mg/dl for 24 h significantly reduced production of NO. Pretreatment with benzbromarone, losartan or irbesartan normalized NO production. The same exposure resulted in dephosphorylation of endothelial NO synthase (eNOS) in HUVECs. Again pretreatment with benzbromarone, losartan or irbesartan abolished this effect., Conclusion: Urate reduced NO production by impaired phosphorylation of eNOS in HUVEC via activation of UATs, which could be normalized by urate lowering agents., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To examine effects of a long-acting calcium channel blocker (CCB) azelnidipine on uric acid metabolism in hypertensive patients., Methods: Azelnidipine was administered to 72 patients at a daily dose of 8 mg or 16 mg. In 22 cases out of the 72 patients, a different CCB was switched to azelnidipine. Blood pressure was measured and biochemical parameters of blood and urine were evaluated before and 2-3 months after the administration., Results: Azelnidipine significantly decreased both systolic and diastolic blood pressure and the heart rate. It decreased both serum urate levels and the urinary uric acid to creatinine ratio (Uur/Ucr), but did not affect the uric acid clearance to creatinine clearance ratio (Cur/Ccr). Azelnidipine decreased both Uur/Ucr and Cur/Ccr in patients with Uur/Ucr ≥ 0.5 or ≥ 0.34, although it did not change these clearance parameters in patients with Uur/Ucr <0.5 or <0.34. Azelnidipine decreased the serum urate levels and Uur/Ucr in hyperuricemic patients with uric acid levels ≥ 7.0 mg/dL in males and ≥ 6.0 mg/dL in females. It did not change these parameters in normouricemic patients with serum urate levels <7.0 mg/dL in males and <6.0 mg/dL in females. Azelnidipine decreased Uur/Ucr and Cur/Ccr in hyperuricemic patients with normal or over excretion of uric acid, although it did not change these clearance parameters in hyperuricemic patients with uric acid hypoexcretion., Conclusions: Azelnidipine decreased the serum urate acid levels and Uur/Ucr, and this response was most prominent in hyperuricemic patients or patients with normal and over excretion of uric acid.

Although nonvasodilating β1 blockers increase the levels of uric acid in serum, it is not known whether vasodilating β1 blockers have a similar effect. In the present study, we evaluated the effect of celiprolol on the release of hypoxanthine, a uric acid precursor, from muscles after an exercise. We used the semi-ischemic forearm test to examine the release of lactate (ΔLAC), ammonia (ΔAmm), and hypoxanthine (ΔHX) before and 4, 10, and 60 min after an exercise in 18 hypertensive patients as well as 4 normotensive subjects. Before celiprolol treatment, all the levels of ΔHX and ΔAmm, and ΔLAC were increased by semi-ischemic exercise in hypertensive patients, and the increases were remarkably larger than those in normotensive subjects. Celiprolol decreased both systolic and diastolic pressure. It also decreased the levels of ΔHX and ΔAmm without changes in ΔLAC after an exercise. These findings also were confirmed by summation of each metabolite (ΣΔMetabolites). Celiprolol caused a marginal decrease of serum uric acid, but the difference was not statistically significant. On the other hand, nonvasodilating β1 blockers did not suppress the levels of ΔHX and ΔAmm, whereas they significantly increased ΔLAC after an exercise. Celiprolol improved energy metabolism in skeletal muscles. It suppressed HX production and consequently did not adversely affect serum uric acid levels., (© Georg Thieme Verlag KG Stuttgart · New York.)

The effects of cilnidipine on the serum uric acid level and urinary NO excretion in hypertensive patients were investigated. Blood and urine samples of 16 hypertensive outpatients were collected before and 2 months after cilnidipine therapy (10 mg). The serum uric acid level decreased significantly after cilnidipine treatment, while the uric acid-creatinine clearance ratio was unaffected. The cilnidipine medication produced a significant increase in urinary NO excretion, although amlodipine did not change it significantly. Therefore, cilnidipine has a profound antihypertensive effect and may reduce the serum uric acid level and increase NO production in the kidney.

In hypertensive subjects, their serum uric acid levels tend to be higher because of decreasing urinary secretion or overproduction of uric acid. Among calcium channel blockers (CCBs) , long acting nifedipine and cilnidipine reveal serum uric acid lowering action. They decrease the production of uric acid precursor in skeletal muscles under anaerobic condition induced by hypertension or insulin resistance. Hyperuricemia is considered to be a risk factor of not only gout but also renal and cardiovascular diseases, thus, it is important to use CCBs without adverse effect on uric acid metabolisms.

Background: A combination therapy of a low-dose antihypertensive diuretic with an angiotensin II receptor blocker (ARB) may have unfavorable effects on serum urate levels., Methods: Forty-two hypertensive patients without hyperuricemia (18 men and 24 women, mean age 65 years) were randomly divided into three groups. Each of the group was allocated to a combination therapy with losartan (LOS; CAS 124750-99-8; 50 mg/day)/hydrochlorothiazide (HCTZ; CAS 58-93-5; 12.5 mg/day) (LOS/HCTZ group), telmisartan (TEL; CAS 144701-48-4; 40 mg/day)/HCTZ (12.5 mg/day) (TEL/HCTZ group), or candesartan (CND; CAS 145040-37-5; 8 mg/day)/HCTZ (12.5 mg/day) (CND/HCTZ group), respectively. Before and after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated., Results: Both systolic and diastolic blood pressures significantly decreased in all groups (p < 0.01) without any statistical differences. The LOS/HCTZ group showed no changes in serum urate levels (5.8 +/- 1.0 mg/dl to 5.8 +/- 1.4 mg/dl) and in % fractional excretion of urate (FEUA). In the TEL/HCTZ group, the serum urate level was significantly increased, from 5.5 +/- 0.9 mg/dl to 6.5 +/- 1.2 mg/dl (p < 0.01), whereas FEUA significantly decreased (p < 0.01). Similarly, the CND/HCTZ group showed a significant increase in the serum urate level from 5.4 +/- 0.9 mg/dl to 6.0 +/- 1.2 mg/dl (p < 0.01) and a significant decrease in FEUA (p < 0.01). No significant differences were found in fasting plasma glucose and electrolytes levels in any of the groups., Conclusions: A combination therapy with a low-dose HCTZ and ARBs resulted in reduced urate excretion and elevated serum urate levels. A combination therapy with the ARB losartan was not accompanied with these effects, likely because of its inhibitory action on urate transporter 1. The study limitations deserve mention in consideration of ethic restrictions, small size, short term examination and uncontrolled design.

Idiopathic hyperuricemia is generally defined as hyperuricemia caused by unknown origin. Idiopathic hyperuricemia is categorized as overproducing or underexcretion of uric acid. Overproduced uric acid is caused by increased biosynthesis of purine bodies, hypermetabolization of purine bodies, or increased intake of dietary purine bodies. Idiopathic hyperuricemia with overproducing uric acid can be diagnosed by amount of excreted uric acid in the urine. Recently it has been identified that hypertension are frequently associated with myogenic hyperuricemia converted from overproduced hypoxanthine in the skeletal muscles. Some anti-hypertensive drugs including alpha1 blocker, ACE inhibitor, alphabeta blocker, or long-acting Ca blocker attenuated the myogenic hyperuricemia. Thus, these drugs may be helpful in the management of hypertension with hyperuricemia.

Although nonvasodilating β1 blockers increase the levels of uric acid in serum, it is not known whether vasodilating β1 blockers have a similar eff ect. In the present study, we evaluated the eff ect of celiprolol on the release of hypoxanthine, a uric acid precursor, from muscles after an exercise. We used the semi-ischemic forearm test to examine the release of lactate (▵ LAC), ammonia (▵ Amm), and hypoxanthine (▵ HX) before and 4, 10, and 60 min after an exercise in 18 hypertensive patients as well as 4 normotensive subjects. Before celiprolol treatment, all the levels of ▵ HX and ▵ Amm, and ▵ LAC were increased by semi-ischemic exercise in hypertensive patients, and the increases were remarkably larger than those in normotensive subjects. Celiprolol decreased both systolic and diastolic pressure. It also decreased the levels of ▵ HX and ▵ Amm without changes in ▵ LAC after an exercise. These fi ndings also were confi rmed by summation of each metabolite (Σ▵ Metabolites). Celiprolol caused a marginal decrease of serum uric acid, but the diff erence was not statistically signifi cant. On the other hand, nonvasodilating β1 blockers did not suppress the levels of ▵ HX and ▵ Amm, whereas they signifi cantly increased ▵ LAC after an exercise. Celiprolol improved energy metabolism in skeletal muscles. It suppressed HX production and consequently did not adversely aff ect serum uric acid levels. [ABSTRACT FROM AUTHOR]