title: Response of large and small vessels to alpha and beta adrenoceptor stimulation in heart failure: effect of angiotensin converting enzyme inhibition.
abstract: The increased sympathetic drive in chronic heart failure (CHF) might provoke vascular adrenoceptor desensitization, which, together with endothelial dysfunction, could contribute to the altered vasomotor tone seen in CHF. We investigated 1) whether CHF alters the responses mediated by alpha and beta adrenoceptors in small and large peripheral arteries, and 2) the effect of angiotensin-converting enzyme (ACE) inhibition. Rats with CHF (coronary artery ligation) were treated with placebo or the ACE inhibitor lisinopril (10 mg/kg/d) starting 7 days after ligation. Responses to phenylephrine (alpha 1 agonist), salbutamol (beta 2 agonist) as well as acetylcholine (endothelium-dependent), were assessed after 3 months in isolated and pressurized segments of the abdominal aorta, the femoral and the mesenteric arteries. In animals with hemodynamic signs of CHF, neither the vasoconstrictor responses to phenylephrine nor the vasodilator response to salbutamol were affected. In contrast, the dilator response to acetylcholine of both small arteries, but not that of the aorta, was impaired. Furthermore, CHF did not modify vessel structure. While lisinopril did not modify the responses to adrenergic agonists, it normalized the response to acetylcholine. Furthermore, ACE inhibition reduced vascular media cross sectional area and collagen density. Thus, the unchanged arterial responsiveness to adrenoceptor agonists does not indicate any vascular adrenoceptor desensitization, while endothelial dependent vasodilation of small arteries is impaired in CHF. ACE inhibition does not modify the response to adrenergic stimuli, prevents endothelial dysfunction and induces both cardiac and vascular remodeling, which probably contribute to the effect ACE inhibitors have on exercise tolerance and survival.
authors.affiliation: Department of Pharmacology, VACOMED, IFRMP no 23, Rouen University Medical School, France.
authors.forename: P
authors.initials: P
authors.lastname: Mulder
authors.forename: P
authors.initials: P
authors.lastname: Compagnon
authors.forename: B
authors.initials: B
authors.lastname: Devaux
authors.forename: V
authors.initials: V
authors.lastname: Richard
authors.forename: J P
authors.initials: JP
authors.lastname: Henry
authors.forename: L
authors.initials: L
authors.lastname: Elfertak
authors.forename: M C
authors.initials: MC
authors.lastname: Wimart
authors.forename: E
authors.initials: E
authors.lastname: Thibout
authors.forename: E
authors.initials: E
authors.lastname: Comoy
authors.forename: B
authors.initials: B
authors.lastname: Macé
authors.forename: C
authors.initials: C
authors.lastname: Thuillez
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000097:blood; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D018377:Neurotransmitter Agents; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009599:Nitroprusside; D010656:Phenylephrine; D017706:Lisinopril; D000109:Acetylcholine; D000420:Albuterol