CHRONIC ANGIOTENSIN-II TYPE-1 RECEPTOR ANTAGONISM IN GENETIC-HYPERTENSION - EFFECTS ON VASCULAR STRUCTURE AND REACTIVITY

Objective and design: The aim of the study was to assess the role of a ngiotensin II (Ang II) in the maintenance of cardiovascular hypertroph y and the abnormal vascular amplifier properties in spontaneously hype rtensive rats (SHR) with established hypertension. Losartan, a type I Ang II receptor antagonist, was administered to SHR and Wistar-Kyoto ( WKY) rats, and its effects on blood pressure, cardiac hypertrophy, vas cular morphology and hindquarter vascular amplifier properties assesse d at the end of treatment and 3 months later. Methods. Losartan was ad ministered for 6 weeks to 14-week-old SHR (60 mg/kg per day orally). A bio-equivalent dose (20 mg/kg per day orally) was administered to age -matched WKY rats. Systolic blood pressure (SBP) was measured in consc ious rats by tail-cuff plethysmography. Morphological changes were ass essed both in the heart, from the ratio of the weight of the left vent ricular wall plus septum to body weight, and in blood vessels from the medial cross-sectional areas of the abdominal aorta and mesenteric ar teries. Vascular amplifier properties were measured by perfusion of th e rat hindquarters under conditions of full dilation (papaverine hydro chloride) and incremental constriction with methoxamine hydrochloride. Results: Losartan lowered SBP in SHR to normotensive WKY rat levels d uring treatment. Left ventricular hypertrophy and aortic cross-section al area were reduced at the end of treatment to WKY rat levels; mesent eric artery cross-sectional area was reduced to a lesser extent. The a bnormal hindquarter vascular amplifier properties of the SHR were norm alized by losartan. Three months after treatment ended, SBP had return ed to untreated SHR levels. Left ventricular hypertrophy and the abnor mal hindquarter vascular amplifier properties had also partially redev eloped. Conclusions: Our findings support the hypothesis that Ang II c ontributes to the maintenance of cardiovascular hypertrophy and the ab normal vascular amplifier properties in SHR with established hypertens ion. However, its role appears to be variable and to depend on the typ e of vascular bed. Other, pressure-independent, factors may also contr ibute to vascular hypertrophy.