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 by increased levels of angiotensin II or by increased blood pressure. SHR were treated from 7 to 15 weeks of age with perindopril to block the in vivo production of A II and concomitantly infused with either a pressor dose of norepinephrine or angiotensin II. At the end of the treatment period, there was no significant difference in the systolic blood pressure in the norepinephrine or angiotensin II-treated groups (201 +/- 9 and 208 +/- 8 mm Hg, respectively). However, there was a significant increase (p < 0.01) in left ventricle-plus-septum/body weight ratio in angiotensin II compared with norepinephrine-infused SHR (3.72 +/- 0.25 and 2.34 +/- 0.04 mg/g, respectively) and in aortic medial cross-sectional area (0.55 +/- 0.05 and 0.38 +/- 0.01 mm2, respectively). Using an unbiased optical dissector/fractionator technique, the number of smooth muscle cells in the descending thoracic aorta of the angiotensin II-infused SHR was not different from norepinephrine-infused rats (5.02 +/- 0.30 x 10(6) and 4.71 +/- 0.42 x 10(6) cells, respectively), and no difference in size of enzyme-isolated cells was observed (mode: 1,326 +/- 127 microns 3 compared with 1,186 +/- 82 microns 3). The results indicate that angiotensin II directly stimulates cardiac and aortic hypertrophy 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 an increase in the extracellular compartment.
Black
M J
MJ
Baker Medical Research Institute, Melbourne, Victoria, Australia.
Campbell
J H
JH
Campbell
G R
GR
D000804:Angiotensin II / Q000032:analysis / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006984:Hypertrophy / Q000209:etiology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D000804:Angiotensin II; D020913:Perindopril