EFFECT OF PERINDOPRIL ON CARDIOVASCULAR HYPERTROPHY OF THE SHR - RESPECTIVE ROLES OF REDUCED BLOOD-PRESSURE AND REDUCED ANGIOTENSIN-II LEVELS

The aim was to determine whether cardiovascular hypertrophy in primary hypertension in the spontaneously hypertensive rat (SHR) is induced b y increased levels of angiotensin II or by increased blood pressure. S HR were treated from 7 to 15 weeks of age with perindopril to block th e in vivo production of A II and concomitantly infused with either a p ressor dose of norepinephrine or angiotensin II. At the end of the tre atment period, there was no significant difference in the systolic blo od pressure in the norepinephrine or angiotensin II-treated groups (20 1 +/- 9 and 208 +/- 8 mm Hg, respectively). However, there was a signi ficant increase (p < 0.01) in left ventricle-plus-septum/body weight r atio in angiotensin II compared with norepinephrine-infused SHR (3.72 +/- 0.25 and 2.34 +/- 0.04 mg/g, respectively) and in aortic medial cr oss-sectional area (0.55 +/- 0.05 and 0.38 +/- 0.01 mm2, respectively) . Using an unbiased optical dissector/fractionator technique, the numb er of smooth muscle cells in the descending thoracic aorta of the angi otensin II-infused SHR was not different from norepinephrine-infused r ats (5.02 +/- 0.30 x 10(6) and 4.71 +/-0.42 x 10(6) cells, respectivel y), and no difference in size of enzyme-isolated cells was observed (m ode: 1,326 +/- 127 mum3 compared with 1,186 +/- mum3). The results ind icate that angiotensin II directly stimulates cardiac and aortic hyper trophy through a mechanism unrelated to its effect on blood pressure. The aortic hypertrophy is not due to an increase in smooth muscle cell size or number and thus must be related to and increase in the extrac ellular compartment.