In a double-blind randomized trial, the effects of treatment with an angiotensin-converting enzyme (ACE) inhibitor (perindopril) and a beta-blocker (atenolol) on small artery structure were compared in previously untreated essential hypertensive patients. Subjects (diastolic blood pressure > or = 100 and < or = 120 mm Hg) were randomly assigned to treatment for 12 months with either perindopril (n = 13, 4 to 8 mg/d) or atenolol (n = 12, 50 to 100 mg/d); the dosage was adjusted upward and in some cases combined (n = 5, perindopril; n = 2, atenolol) with thiazide diuretic to achieve target blood pressure (diastolic blood pressure below 90 mm Hg). Before and at the end of treatment, gluteal biopsies were taken under local anesthetic; from these biopsies, two small arteries were dissected and mounted on a myograph for morphometry. The reduction in blood pressure with atenolol (drop in mean blood pressure 28.4 +/- 1.8 mm Hg) was greater than with perindopril (20.6 +/- 1.8 mm Hg, P < .05). Perindopril treatment caused an increase in small artery diameter (231 +/- 14 to 274 +/- 13 microns, P < .05) and a reduction in the ratio of media thickness to lumen diameter (7.94 +/- 0.65% to 5.96 +/- 0.42%, P < .05), whereas atenolol had no effect (246 +/- 14 to 231 +/- 13 microns and 7.14 +/- 0.47% to 6.79 +/- 0.45%, respectively). The change in small artery morphology caused by perindopril was not accompanied by any change in media cross-sectional area, suggesting that the change was due to "remodeling."(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal resistance artery structure independently predicts cardiovascular events in essential hypertensive patients at moderate risk.

Long-term treatment of young spontaneously hy-pertensive rats (SHR) with angiotensin-converting enzyme (ACE) inhibitors has a persistent effect on blood pressure when treatment is withdrawn. The aim of the present study was to determine whether this effect could be mediated by the effect of treatment on resistance-artery structure. We determined the dose dependence of ACE-inhibitor therapy on blood pressure and small-artery structure during treatment and on the recovery of blood pressure when treatment was withdrawn. SHR (40 per group) were treated from age 4 to 24 weeks with one of three doses of perindopril (0.4, 0.8, or 1.5 mg/kg per day). Control groups were untreated SHR and Wistar-Kyoto rats. At 24 weeks, treatment was stopped and small arteries were taken from half of the rats from the mesenteric, femoral, cerebral, and coronary vascular beds for morphological and functional measurements. The blood pressure of the other half of the rats was followed until 36 weeks of A lthough modern antihypertensive treatment is in / \ general able to control blood pressure, it is _Z \. almost invariably found that withdrawal of treatment results in blood pressure returning to original hypertensive levels in both essential hypertensive patients 13 and animal models of hypertension. 46 A notable exception to this rule concerns treatment of young spontaneously hypertensive rats (SHR) with angioten-sin-converting enzyme (ACE) inhibitors, in which, after treatment is discontinued, blood pressure remains at a level below that of control SHR. 610 This persistent effect of ACE inhibitor treatment seems to be mediated through the ability of ACE inhibitors to reduce angio-tensin II levels, for similar results are obtained with the angiotensin II receptor inhibitor losartan. 11 There is also evidence that the effect is only seen if the treatment is performed while animals are young. 7 Given the fact that the pathogenesis of hypertension in SHR might have relevance for some forms of human essential hypertension, it is clear that elucidation of the mechanism of the persistent effect could provide an interesting new therapeutic approach. One possible mechanism concerns vascular structure because, on the basis that an increased media-lumen ratio of resistance vessels could be a factor that maintains hyperten-sion, 1213 reduction of the media-lumen ratio could maintain low pressure levels. This possibility has been age. During treatment, perindopril caused a dose-dependent reduction in blood pressure and in the media-lumen ratio and media area of the small arteries, whereas there was a dose-dependent increase in lumen diameter. The effect of treatment on the structure of arteries from the different vascular beds was homogeneous. Compared with values from Wistar-Kyoto rats, blood pressure normalization in SHR was not associated with full normalization of structure. After withdrawal of treatment, there was an inverse relation between perindopril dose and the persistent effect. The results suggest that although treatment of SHR has a unif...

On-treatment small artery structure identifies individuals still at increased cardiovascular risk despite long-term BP normalization and may be an additional target for therapy to prevent cardiovascular events.

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