Evidence that lacidipine at nonsustained antihypertensive doses activates nitrogen monoxide system in the endothelium of salt-loaded Dahl-S rats.
Lacidipine is a clinically active, antihypertensive calcium antagonist of the 1,4 dihydropyridine (DHP) class. It is also capable of vascular protection when administered (prophylactically and therapeutically) at nonsustained antihypertensive doses to salt-sensitive Dahl-S rats: useful animal models for studying the vasoprotective effect of calcium antagonists. In our previous work using voltammetry with selective biosensors, we observed that lacidipine implements endothelial nitrogen monoxide (NO) in normal rats. These experiments, performed in aortic rings obtained from Dahl-S rats analyzed with voltammetry and specific biosensors, further demonstrate that lacidipine, given at doses that do not control the development of hypertension (1 mg/kg), enhance endothelial NO activity. Taken together with the observation that 1 mg/kg lacidipine, and not its vehicle, is able to prevent vascular damage and concomitant increases in mortality (accelerated by a salt diet), this voltametric data suggest that NO acts as a component of positive influence of this DHP on vascular structure and function.
Crespi
Francesco
F
Department of Biology, GlaxoSmithKline Group, GlaxoWellcome, S. p. A. Medicine Research Centre, Via Fleming 4, 37100 Verona, Italy. fc20377@gsk.com
Vecchiato
Elena
E
Lazzarini
Chiara
C
Andreoli
Michela
M
Gaviraghi
Giovanni
G
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004563:Electrochemistry; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017673:Sodium Chloride, Dietary; C060285:lacidipine; D009569:Nitric Oxide