title: Coronary dilatation reserve in experimental hypertension and chronic heart failure: effects of blockade of the renin-angiotensin system.
abstract: 1. The aim of the present study was to investigate left and right ventricular (LV and RV, respectively) coronary vasodilatation reserve (CVR; fluorescent microsphere technique) in rats with hypertension (spontaneously hypertensive rats (SHR)) or congestive heart failure (CHF) and the effects of early and chronic renin-angiotensin system (RAS) blockade thereupon. 2. In adult SHR, both LV and RV CVR were impaired, especially in the non-hypertrophied RV, the main factor involved being coronary vascular remodelling. Blockade of the RAS normalized both LV and RV CVR, mainly through the prevention of hypertension and suppression of the resulting pericoronary fibrosis. 3. In postischaemic CHF rats, there was an early and severe degradation of LV and RV CVR that developed before any significant vascular remodelling and appeared to be linked to the deterioration of cardiac hypertrophy and haemodynamics. This degradation in CVR further worsened over the longer term due to late-developing pericoronary fibrosis and endothelial dysfunction. Blockade of the RAS had no early effects on LV and RV CVR, but improved RV CVR over the long term, mainly by limiting RV hypertrophy and by preventing the development of pericoronary fibrosis and coronary endothelial dysfunction. 4. In kallikrein-kinin system-deficient mice, CVR was not different from that of wild-type mice, suggesting that this system is not implicated in normal CVR regulation.
authors.affiliation: Département de Pharmacologie et INSERM 00-01, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France. christine.giudicelli@kb.u-psud.fr
authors.forename: C
authors.initials: C
authors.lastname: Richer
authors.forename: V
authors.initials: V
authors.lastname: Domergue
authors.forename: M
authors.initials: M
authors.lastname: Gervais
authors.forename: P
authors.initials: P
authors.lastname: Fornes
authors.forename: F
authors.initials: F
authors.lastname: Trabold
authors.forename: J F
authors.initials: JF
authors.lastname: Giudicelli
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology; D003331:Coronary Vessels / Q000473:pathology* / Q000503:physiopathology; D017353:Gene Deletion; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology; D000077405:Irbesartan; D016234:Kallikrein-Kinin System / Q000502:physiology; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D013777:Tetrazoles; D007610:Kallikreins; D000077405:Irbesartan; D020913:Perindopril