Effects of chronic treatment with simvastatin on endothelial dysfunction in spontaneously hypertensive rats

J Hypertens. 1999 Jun;17(6):769-76. doi: 10.1097/00004872-199917060-00008.


Objective: To investigate the effects of chronic treatment with simvastatin (SV) on endothelium-dependent relaxation and ouabain-induced contractions in aortic rings from spontaneously hypertensive rats (SHR), comparing with normotensive Wistar-Kyoto rats (WKY).

Methods: After a 12-week period of administration of 1 or 2 mg/kg SV to SHR and WKY, systolic blood pressure (SBP) and vascular reactivity in endothelium-intact aortic rings were assessed.

Results: Relaxation in response to acetylcholine (ACh) in WKY remained unaltered, but in SHR treated with 1 mg/kg SV, enhanced ACh-induced relaxation (P<0.05 versus untreated SHR) reached values observed in untreated WKY. The 2 mg/kg treatment also improved ACh relaxation (P<0.01 and P<0.05 versus untreated SHR and WKY respectively). Inhibiting cyclo-oxygenase (COX) with indomethacin (INDO) improved ACh relaxation in SHR (P<0.05) but not in WKY, independent of treatment with SV. Inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine (L-NOARG) abolished ACh relaxations in all cases (P<0.001). The result was unaltered when combining INDO plus L-NOARG. SV treatment also decreased ouabain-induced contractions in endothelium-intact aortic rings from SHR, diminishing the percentage effect of contraction from 64.56+/-2.95 (untreated SHR) to 26.98+/-7.06 and 38.10+/-8.21 (1 and 2 mg/kg treated SHR respectively). Response to ouabain in WKY was not significantly affected by SV treatment

Conclusions: Chronic treatment of SHR with SV improves endothelium-dependent ACh relaxation of the aortic rings, probably by an NO-involving mechanism more than by inhibiting contractile COX-derived factors. An improvement in endothelial modulation of ouabain-induced contractions was also observed after treatment with SV in SHR, which might be due to an inhibition of a calcium-sodium exchanger.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / enzymology
  • Aorta, Thoracic / physiopathology
  • Blood Pressure / drug effects
  • Cardiotonic Agents / pharmacology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Follow-Up Studies
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypertension / drug therapy*
  • Hypertension / enzymology
  • Hypertension / physiopathology
  • Male
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • Ouabain / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Simvastatin / therapeutic use*
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology


  • Cardiotonic Agents
  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Vasodilator Agents
  • Nitroarginine
  • Ouabain
  • Simvastatin
  • Nitric Oxide Synthase
  • Acetylcholine