The 5-HT2 receptor antagonist sarpogrelate reduces urinary and plasma levels of thromboxane A2 and urinary albumin excretion in non-insulin- dependent diabetes mellitus patients

Susumu Ogawa, Kazuhisa Takeuchi, Kazuhiko Sugimura, Chiharu Sato, Motoshi Fukuda, Ribun Lee, Sadayoshi Ito, Tokutaro Sato

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23 Citations (Scopus)

Abstract

1. Therapeutic effects of a 5-HT2 receptor antagonist sarpogrelate on microalbuminuria and thromboxane (TX)A2 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 TXB2 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 TXB2 and urinary TXB2 excretion were significantly decreased. In contrast, in the untreated group (group F), neither plasma levels TXB2 nor urinary TXB2 excretion was changed. 6. In conclusion, microalbuminuria was improved by treatment with the 5-HT2 receptor antagonist sarpogrelate independent of latent vasculopathy. Blockade of 5-HT2 receptors is suggested to be beneficial for the treatment of nephropathy in NIDDM patients. It is possible that the inhibition of TXA2 biosynthesis is involved in the therapeutic effect of 5-HT2 receptor antagonists.

Original languageEnglish
Pages (from-to)461-464
Number of pages4
JournalClinical and Experimental Pharmacology and Physiology
Volume26
Issue number5-6
DOIs
Publication statusPublished - 1999 Jul 13

Keywords

  • Diabetes
  • Sarpogrelate
  • Serotonin
  • Thromboxane
  • Urinary albumin

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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