Effects of chronic converting enzyme inhibition on the structure and function of large arteries in the rat.
The effects of renovascular hypertension and its treatment by a converting enzyme inhibitor (perindopril) on the structure and function of large arteries were studied in the Goldblatt 1 clip--2 kidney rat. One month after the surgical operation, the hypertensive animals (n = 24) and the sham operated animals (n = 24) were divided into two groups receiving either 1 mg/kg per day of perindopril or distilled water for four weeks. At the end of treatment, the hemodynamic parameters, including blood pressure and instantaneous blood flow measured by Doppler, were measured in anesthetized rats. The mechanical properties of the carotid artery were studied by in situ measurement of the carotid compliance in response to imposed pressures. Lastly, morphometric parameters of the thoracic aorta, including the thickness of the media, the density of elastin, collagen and nuclei and the area of the nuclei were studied by an automated image analysis system. Hypertension was associated with an increase in the characteristic impedance of the aorta (14,479 +/- 5,171 vs 9,022 +/- 4,071 dyne.sec/cm5; p less than 0.01) and a reduction in systemic arterial compliance (2.41 +/- 0.96 vs 3.92 +/- 1.15 x 10(-3) ml/mmHg; p less than 0.01) or carotid arterial compliance (6.31 +/- 1.85 vs 8.38 +/- 3.14 x 10(-2) mm3/mmHg; p less than 0.05). Treatment with perindopril normalized systolic and diastolic blood pressure and completely inverted the markers of rigidity of the large arteries. Morphometric analysis of the aortic wall allowed these functional modifications to be attributed to structural modifications of the wall. The thickness of the media was increased by hypertension (122.3 +/- 3.7 vs 97.5 +/- 4.4 microns; p less than 0.01). This thickening was attributed to hypertrophy of the smooth muscle cells as evidenced by the increase in the nucleus size (8.58 +/- 1.54 vs 7.38 +/- 0.78 microns 2; p less than 0.01). It was accompanied by an increase in the density of collagen (8.6 +/- 3.6 vs 7.3 +/- 2.4%; p less than 0.01) and a decrease in the density of elastin (31.9 +/- 8.3 vs 38.6 +/- 12.8%; p less than 0.01). Treatment with perindopril normalized the thickness of the media (103.0 +/- 4.8 microns) by reducing cellular hypertrophy. The short duration of treatment did not allow regression of the modifications in the density of the proteins of the interstitial matrix. In conclusion, renovascular hypertension severely alters the functional and structural properties of large arteries. Treatment with perindopril normalizes the properties of the vessel wall.(ABSTRACT TRUNCATED AT 400 WORDS)
Levy
B I
BI
INSERM Unité 141, Hôpital Lariboisière, Paris.
Michel
J B
JB
Salzmann
J L
JL
Devissaguet
M
M
Camilleri
J P
JP
Safar
M E
ME
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001158:Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology*; D020913:Perindopril; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril