title: Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives.
abstract: Hypertension and diabetes are associated with an increased arterial stiffness. A direct blood pressure-independent effect of angiotensin-converting enzyme inhibitors on arterial stiffness has never been unequivocally demonstrated. In this mechanistic study, we used an experimental design in which patients responding to 1 month treatment with 4 mg perindopril were randomized double-blind to either 4 mg perindopril or 8 mg perindopril for 6 months. We determined carotid distensibility with echotracking and applanation tonometry at baseline and after the 7-month treatment period in 57 essential hypertensive patients with type 2 diabetes (age 63+/-7 years). We monitored ambulatory blood pressure at baseline and after treatment. After 7 months treatment, 24-hour ambulatory blood pressure significantly decreased, with no significant difference between 4 mg and 8 mg perindopril. Carotid distensibility increased more after 8 mg perindopril compared with 4 mg perindopril (8 mg: from 13.1+/-5.9 to 16.0+/-6.7 kPa(-1)x10(-3); 4 mg: from 13.2+/-5.2 to 12.7+/-5.9 kPa(-1)x10(-3); ANOVA, dose-period interaction, P<0.05). Carotid internal diameter and elastic modulus were significantly lower after 8 mg perindopril compared with 4 mg perindopril, independent of blood pressure reduction. These results indicate a dose-dependent and blood pressure-independent reduction in carotid stiffness under chronic treatment with an angiotensin-converting enzyme inhibitor. They suggest that arterial distensibility was increased through an inward remodeling, leading to a reduction in wall stress, thus reducing elastic modulus. They also suggest that long-term administration of high doses (8 mg) of perindopril is required to improve carotid structure and function in hypertensive patients with type 2 diabetes.
authors.affiliation: Department of Pharmacology and INSERM U 652, Georges Pompidou European Hospital, Paris, France.
authors.forename: Anne-Isabelle
authors.initials: AI
authors.lastname: Tropeano
authors.forename: Pierre
authors.initials: P
authors.lastname: Boutouyrie
authors.forename: Bruno
authors.initials: B
authors.lastname: Pannier
authors.forename: Robinson
authors.initials: R
authors.lastname: Joannides
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Balkestein
authors.forename: Sandrine
authors.initials: S
authors.lastname: Katsahian
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laloux
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Harry
authors.initials: H
authors.lastname: Struijker-Boudier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Laurent
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D048909:Diabetes Complications / Q000473:pathology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril