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 angiotensin II (Ang II) in the maintenance of cardiovascular hypertrophy and the abnormal vascular amplifier properties in spontaneously hypertensive 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, vascular morphology and hindquarter vascular amplifier properties assessed at the end of treatment and 3 months later. Methods. Losartan was administered 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 conscious rats by tail-cuff plethysmography. Morphological changes were assessed both in the heart, from the ratio of the weight of the left ventricular wall plus septum to body weight, and in blood vessels from the medial cross-sectional areas of the abdominal aorta and mesenteric arteries. Vascular amplifier properties were measured by perfusion of the rat hindquarters under conditions of full dilation (papaverine hydrochloride) and incremental constriction with methoxamine hydrochloride. Results: Losartan lowered SBP in SHR to normotensive WKY rat levels during treatment. Left ventricular hypertrophy and aortic cross-sectional area were reduced at the end of treatment to WKY rat levels; mesenteric artery cross-sectional area was reduced to a lesser extent. The abnormal hindquarter vascular amplifier properties of the SHR were normalized by losartan. Three months after treatment ended, SBP had returned to untreated SHR levels. Left ventricular hypertrophy and the abnormal hindquarter vascular amplifier properties had also partially redeveloped. Conclusions: Our findings support the hypothesis that Ang II contributes to the maintenance of cardiovascular hypertrophy and the abnormal vascular amplifier properties in SHR with established hypertension. However, its role appears to be variable and to depend on the type of vascular bed. Other, pressure-independent, factors may also contribute to vascular hypertrophy.