Chronic Treatment with the CA2+Channel Inhibitor RO 40-5967 Potentiates Endothelium-Dependent Relaxations in the Aorta of the Hypertensive Salt Sensitive Dahl Rat

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Abstract
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/1; 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.