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)

Left ventricular hypertrophy is a common clinical feature in hypertensive patients and may be associated with structural changes in vessel morphology. In an open prospective trial, we evaluated 14 patients with previously untreated hypertension (163 +/- 2/104 +/- 2 mm Hg) and an echocardiographically determined left ventricular mass index of 141.6 +/- 5.2 g/m2, indicating left ventricular hypertrophy. We obtained a gluteal skin biopsy sample before starting treatment to investigate subcutaneous small-artery (approximately 200 to 400 microns diameter) morphology and function. Patients then received antihypertensive treatment with a combination of spirapril (3 or 6 mg) and isradipine (2.5 or 5 mg). Echocardiographic recordings were made after 6 months and 1 year, and a final biopsy was taken after 1 year. After 1 year, blood pressure was significantly reduced to 142 +/- 3/ 90 +/- 1 mm Hg (P < .001), and left ventricular mass index decreased significantly to 105.3 +/- 5.8 g/m2 (P < .001). Baseline media-lumen ratio (7.64 +/- 0.48%) was not markedly reduced (7.21 +/- 0.55%), although a decrease occurred in 7 of 12 evaluable patients. Norepinephrine-induced vasoconstriction was markedly reduced after 1 year. In conclusion, a significant regression of left ventricular hypertrophy was obtained after 1 year of treatment with spirapril and isradipine, whereas a similar reduction in medial thickness relative to lumen diameter of subcutaneous small arteries could not be observed in all patients. Reversal of structural changes in resistance vessels may require a longer treatment period in patients with proven left ventricular hypertrophy.

The structure and function of subcutaneous small arteries from patients with mild heart failure ( n = 27) 6–43 mo after myocardial infarction were compared with vessels from healthy control subjects ( n = 10). Patients were randomized to treatment with placebo or the angiotensin-converting enzyme inhibitor ramipril starting 3–10 days after myocardial infarction. Dissected arterial vessels were mounted on a wire myograph for measurement of morphology and isometric tension. Morphology was not different in arteries from the three groups. Responses to norepinephrine, angiotensin II, and electrical field stimulation were similar in arteries from placebo-treated patients with mild heart failure and control subjects. Similarly, endothelium-dependent and -independent relaxation was normal in arteries from patients with mild heart failure. Ramipril therapy was associated with functional alterations: vasoconstrictor responses to norepinephrine and angiotensin II were significantly enhanced compared with placebo ( P < 0.001). These data suggest that vascular structure and function are not different in vitro in subcutaneous arteries from placebo-treated patients with mild heart failure. Angiotensin-converting enzyme inhibitor therapy is associated with enhanced vasoconstriction to norepinephrine and angiotensin II, which may reflect upregulation of receptor-mediated events.