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THE 5‐HT 2 RECEPTOR ANTAGONIST SARPOGRELATE REDUCES URINARY AND PLASMA LEVELS OF THROMBOXANE A 2 AND URINARY ALBUMIN EXCRETION IN NON‐INSULIN‐DEPENDENT DIABETES MELLITUS PATIENTS †
Author(s) -
Ogawa Susumu,
Takeuchi Kazuhisa,
Sugimura Kazuhiko,
Sato Chiharu,
Fukuda Motoshi,
Lee Ribun,
Ito Sadayoshi,
Sato Tokutaro
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1999.03056.x
Subject(s) - medicine , microalbuminuria , endocrinology , albuminuria , thromboxane , excretion , diabetes mellitus , albumin , renal function , proteinuria , diabetic nephropathy , platelet , kidney
1. Therapeutic effects of a 5‐HT 2 receptor antagonist sarpogrelate on microalbuminuria and thromboxane (TX)A 2 biosynthesis were examined in non‐insulin‐dependent diabetes mellitus (NIDDM) patients. 2. In protocol I, the ankle‐brachial pressure index (API; an indicator of peripheral blood flow) and urinary albumin excretion (U alb V; an indicator of renal function) were determined in 42 NIDDM patients who had been treated with 300 mg/day sarpogrelate for 8 weeks. In an analysis of the results, the NIDDM patients were divided into four groups based on the severity of either vasculopathy or nephropathy as follows: group A, API < 0.9, U alb V ≥ 100 mg/day; group B, API < 0.9, U alb V < 100 mg/day; group C API ≥ 0.9, U alb V ≥ 100 mg/day; and group D, API ≥ 0.9, U alb V < 100 mg/day. 3. In protocol II, 10 NIDDM patients with U alb V values > 100 mg/day were divided into two groups to further confirm the effect of sarpogrelate on albuminuria: group E, the sarpogrelate treatment group ( n = 5); and group F, the no treatment group ( n = 5). 4. In protocol I, the incidence of a cold sensation in the lower extremities was reduced from 45.2 to 21.4% following sarpogrelate treatment. In patients with U alb V ≥ 100 mg/day (groups A and C), U alb V was significantly decreased independent of API, while it did not change in patients with U alb V < 100 mg/day (groups B and D). Plasma TXB 2 levels were significantly decreased following sarpogrelate treatment, whereas plasma 6‐keto‐prostaglandin F 1α levels were not. 5. In protocol II, in the sarpogrelate treatment group (group E), albuminuria was significantly improved and both plasma levels TXB 2 and urinary TXB 2 excretion were significantly decreased. In contrast, in the untreated group (group F), neither plasma levels TXB 2 nor urinary TXB 2 excretion was changed. 6. In conclusion, microalbuminuria was improved by treatment with the 5‐HT 2 receptor antagonist sarpogrelate independent of latent vasculopathy. Blockade of 5‐HT 2 receptors is suggested to be beneficial for the treatment of nephropathy in NIDDM patients. It is possible that the inhibition of TXA 2 biosynthesis is involved in the therapeutic effect of 5‐HT 2 receptor antagonists.