Chronic treatment with the CA2+ channel inhibitor RO 40-5967 potentiates endothelium-dependent relaxations in the aorta of the hypertensive salt sensitive Dahl rat.
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.
Boulanger
C M
CM
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas 77030.
Desta
B
B
Clozel
J P
JP
Vanhoutte
P M
PM
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D020748:Mibefradil; D051381:Rats; D011922:Rats, Mutant Strains; D012016:Reference Values; D012965:Sodium Chloride; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D014665:Vasodilator Agents; D020748:Mibefradil; D012965:Sodium Chloride