Effects of fluvastatin on endothelium-derived hyperpolarizing factor- and nitric oxide-mediated relaxations in arteries of hypertensive rats

Yasuo Kansui, Koji Fujii, Kenichi Goto, Isao Abe, Mitsuo Iida

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

1. Endothelial cells release endothelium-derived hyperpolarizing factor (EDHF), as well as nitric oxide (NO). It has recently been suggested that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improve NO-mediated endothelial function, partially independently of their cholesterol-lowering effects. It is, however, unclear whether statins improve EDHF-mediated responses. 2. Eight-month-old stroke-prone spontaneously hypertensive rats (SHRSP) were treated with fluvastatin (10 mg/kg per day) for 1 month. Age-matched, normotensive Wistar Kyoto (WKY) rats served as controls. Both EDHF- and NO-mediated relaxations were impaired in SHRSP compared with WKY rats. 3. Fluvastatin treatment did not affect blood pressure and serum total cholesterol. The acetylcholine (ACh)-induced, EDHF-mediated hyperpolarization in mesenteric arteries did not significantly differ between fluvastatin-treated SHRSP and untreated SHRSP and the responses in both groups were significantly smaller compared with those of WKY rats. Endothelium-derived hyperpolarizing factor-mediated relaxations, as assessed by the relaxation to ACh in mesenteric arteries contracted with noradrenaline in the presence of NG-nitro-L- arginine and indomethacin, were virtually absent and similar in both SHRSP groups. In contrast, NO-mediated relaxation, as assessed by the relaxation in response to ACh in rings contracted witli 77 mmol/L KCl, was improved in fluvastatin-treated SHRSP compared with untreated SHRSP (maximum relaxation in control and fluvastatin groups 42.0 ± 5.2 and 61.2 ± 3.8%, respectively; P < 0.05). 4. Hyperpolarization and relaxation in response to levcromakalim, an ATP-sensitive K+ channel opener, were similar between the two SHRSP groups. 5. These findings suggest that fluvasfatin improves NO-mediated relaxation, but not EDHF-mediated hyperpolarization and relaxation, in SHRSP. Thus, the beneficial effects of the statin on endothelial function may be mainly ascribed to an improvement in the NO pathway, but not EDHF.

Original languageEnglish
Pages (from-to)354-359
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume31
Issue number5-6
DOIs
Publication statusPublished - May 2004

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

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