CardiovascularResearch33(1997)188-195 Ramipril therapy improves arterial dilation in experimental hypertension

Objective:Angiotensin-convertingenzyme(ACE)inhibitionhas been shownto restoreimpairedendothelialfunctionin hypertension, but the rolesof differentmediatorsin enhancedendothelium-dependentdilationhave not been fully characterized.Methods:The effects of ACE inhibitionwith ramipril (1 mg. kg – ‘. day – ) on relaxationresponsesof mesentericarterial rings in vitro were studied in spontaneouslyhypertensiverats (SHR) and normotensiveWistar-Kyotorats (WKY). Results:The 12-week-longtherapy effectively reducedblood pressurein SHR. In noradrenaline(NA)-precontractedarterialrings, endothelium-dependentrelaxationsto acetylcholine (ACh)as well as endothelium-independentdilationsto isoprenalineandnitroprnssideweremorepronouncedin WKYandramipril-treated SHR than in untreated SHR. The cyclo-oxygenaseinhibitor, diclofenac,which reduces the synthesis of dilating and constricting prostanoids,clearlyenhancedthe relaxationto ACh in untreatedSHR,but was withouteffect in the other groups.The nitric oxide(NO) synthaseinhibitor,tVG-nitro-wirgininemethylester(L-NAME),attenuatedthe relaxationsto AChmoreeffectivelyin untreatedSHRthan in the ramipril-SHRand WKY groups.However,when endothelium-dependenthyperpokwizationwas preventedby precontractingthe preparationswith potassiumchloride(KC1),no significantdifferenceswere foundin relaxationsto ACh betweenthe studygroups. In addition,in NA-precontractedrings the diclofenac-and L-NAME-resistantrelaxationsto ACh werepartiallypreventedby glibenclamide and apamin, inhibitors of ATP-dependentand Ca2+-activated K+ channels, respectively.Conclusion:Long-term ACE inhibition normalizedblood pressure and enhancedarterial dilation in SHR. The improvedendothelium-mediatedrelaxationfollowingramipri