Chronic treatment with the CA2+ channel inhibitor RO 40-5967 potentiates endothelium-dependent relaxations in the aorta of the hypertensive salt sensitive Dahl rat

Blood Press. 1994 May;3(3):193-6. doi: 10.3109/08037059409102252.


Experiments were designed to determine whether or not chronic treatment with the Ca2+ channel antagonist RO 40-5967 affects endothelium-dependent relaxations in the aorta of hypertensive, salt-sensitive Dahl rats. Salt-resistant and salt-sensitive Dahl rats were fed a diet containing 8% NaCl (for 8 weeks); in each group, half of the animals were given RO 40-5967 chronically (0.4 mg/l; in the drinking water). RO 40-5967 lowered arterial blood pressure in the salt-sensitive, hypertensive, but not in the salt-resistant, normotensive rats. Rings, with and without endothelium, of thoracic aortas were suspended for isometric tension recording in conventional organ chambers. The chronic treatment with RO 40-5967 potentiated endothelium-dependent relaxations to acetylcholine, adenosine-diphosphate and thrombin in preparations from salt-sensitive, but not in those of salt-resistant Dahl rats. The treatment also augmented, in aortas from salt-sensitive animals, the relaxations of rings without endothelium to the donor of nitric oxide, SIN-1. These experiments demonstrate that chronic administration of RO 40-5967 potentiates endothelium-dependent relaxations in arteries from animals with salt-induced hypertension. This potentiation can be explained in part by an augmented sensitivity of the vascular smooth muscle to endothelium-derived nitric oxide.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Benzimidazoles / pharmacology*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Endothelium, Vascular / physiopathology*
  • Hypertension / chemically induced
  • Hypertension / genetics
  • Hypertension / physiopathology*
  • Male
  • Mibefradil
  • Rats
  • Rats, Mutant Strains
  • Reference Values
  • Sodium Chloride
  • Tetrahydronaphthalenes / pharmacology*
  • Time Factors
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology


  • Benzimidazoles
  • Calcium Channel Blockers
  • Tetrahydronaphthalenes
  • Vasodilator Agents
  • Mibefradil
  • Sodium Chloride