Repair of Coronary Arterioles After Treatment With Perindopril in Hypertensive Heart Disease

Abstract

Abstract-In hypertensive heart disease, no data are available on the repair of coronary resistance vessels in patients after long-term ACE inhibitor treatment. Fourteen patients with essential hypertension were studied with coronary flow reserve and with transvenous endomyocardial biopsy before and after 12 months of antihypertensive treatment with perindopril (4 to 8 mg/d, mean 5.9Ϯ2.3 mg/d). Left ventricular muscle mass index decreased by 11% (from 145Ϯ41 to 128Ϯ36 g/m 2 , Pϭ0.04). Maximal coronary blood flow was increased by 54% (from 170Ϯ46 to 263Ϯ142 mL ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , Pϭ0.001), and minimal coronary vascular resistance was diminished by 33% (from 0.67Ϯ0.21 to 0.45Ϯ0.19 mm Hg ⅐ min ⅐ 100 g ⅐ mL Ϫ1 , Pϭ0.001); consequently, coronary reserve increased by 67% from 2.1Ϯ0.6 to 3.5Ϯ1.9 (Pϭ0.001). Structural analysis revealed regression of periarteriolar collagen area by 54% (from 558Ϯ270 to 260Ϯ173 m 2 , Pϭ0.04) and of total interstitial collagen volume density by 22% (from 5.5Ϯ3.8 Vv% to 4.3Ϯ3.2 Vv%, Pϭ0.04), whereas arteriolar wall area was slightly but not significantly reduced. Long-term therapy with the ACE inhibitor perindopril induces structural repair of coronary arterioles that is mainly characterized by the regression of periarteriolar fibrosis and associated with a marked improvement in coronary reserve. These findings indicate the beneficial reparative effects of ACE inhibition on coronary microcirculation in hypertensive heart disease. (Hypertension. 2000;36:220-225.) Key Words: arterioles Ⅲ collagen Ⅲ hypertension, arterial Ⅲ angiotensin-converting enzyme inhibitors Ⅲ coronary reserve A rterial hypertension is the most common cause of pressure overload of the left ventricle, and left ventricular (LV) hypertrophy (LVH) is its common sequelae. Furthermore, LVH is a strong independent risk factor for cardiovascular morbidity and mortality. 1 Potential mechanisms that might account for this observation include increased vulnerability of the hypertrophied myocardium to ischemic damage and enhanced arrhythmogenesis. 2 Moreover, it is increasingly recognized that patients with arterial hypertension and LVH have symptoms and signs of myocardial ischemia despite angiographically normal coronary arteries, and this was found to be related to impaired coronary flow reserve. 3 Functional and structural abnormalities of the coronary microcirculation have been described in hypertensive heart disease. 4 -6 Thus, an adequate increase in myocardial blood flow may be prevented in response to increased metabolic demand and may precipitate myocardial ischemia in these patients. 7 Important structural components of impaired coronary reserve are thickening of the media wall with reduced lumen size and accumulation of collagen in the periarteriolar region. 4,5 The thickening and hardening of arterioles have been called arteriolosclerosis and are characteristic of pathological hypertensive hypertrophy. 8,9 Antihypertensive treatment has been shown to normalize blood pressure and to reverse LVH in hypertensive patients...

Angiotensin converting enzyme inhibitors for cancer treatment?

“…2,4,[17][18][19][20] Two of these used the PET technique, 2,4 whereas 4 studies used the argon gas chromatography technique. [17][18][19][20] However, using the latter invasive procedure only allows investigation of hypertensive patients with symptoms of ischemia, whereas the PET technique permits investigations of asymptomatic patients, who constitute the majority of the hypertensive population. Furthermore, all studies had in common that antihypertensive treatment was withdrawn before the second measurement of MP.…”

“…11,14,16 The effect of antihypertensive treatment on myocardial perfusion (MP) has been investigated in a number of studies. 2,4,[17][18][19][20] ACE inhibitors 4,19,20 have, with some exceptions, 2 demonstrated reductions in myocardial vascular resistance, which is ascribed to structural repair of coronary arterioles. 20 On this basis it might be expected that the reduced coronary reserve seen in hypertension would be improved by treatment with an ACE inhibitor, but not by a ␤-blocker.…”

“…2,4,[17][18][19][20] ACE inhibitors 4,19,20 have, with some exceptions, 2 demonstrated reductions in myocardial vascular resistance, which is ascribed to structural repair of coronary arterioles. 20 On this basis it might be expected that the reduced coronary reserve seen in hypertension would be improved by treatment with an ACE inhibitor, but not by a ␤-blocker. Improved coronary reserve has been observed previously with ACE inhibition, 4,19,20 but the effect of prolonged ␤-blockade has been studied only to a limited extent.…”

“…20 On this basis it might be expected that the reduced coronary reserve seen in hypertension would be improved by treatment with an ACE inhibitor, but not by a ␤-blocker. Improved coronary reserve has been observed previously with ACE inhibition, 4,19,20 but the effect of prolonged ␤-blockade has been studied only to a limited extent. 17 We have therefore made a direct comparison of the effect of ACE inhibitor and ␤-blocker treatment in patients with essential hypertension.…”

Growing Evidence Linking Microvascular Dysfunction With Heart Failure With Preserved Ejection Fraction

“…These data support a role of coronary microvascular endothelial inflammation and microvascular rarefaction in the pathophysiology of HFpEF. Both microvascular rarefaction and myocardial fibrosis—including perivascular fibrosis, which limits coronary flow reserve18—may uniquely contribute to LV diastolic dysfunction and cardiac reserve function impairment in HFpEF.…”