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Background: Left ventricular hypertrophy constitutes a powerful independent risk factor for heart failure, sudden death and ventricular dysrhythmia. Experimental data suggest that, apart from increased cardiac work load, noradrenaline may be one of the factors triggering myocardial hypertrophy., Objective: To test the hypothesis that the extent of left ventricular hypertrophy is coupled to cardiac noradrenaline independently from the magnitude of arterial blood pressure., Patients and Methods: Following exclusion of coronary artery disease by cardiac catheterization, cardiac noradrenaline release was measured in relation to left ventricular mass in 25 patients with arterial hypertension (HT), of whom five had left ventricular hypertrophy (HT + LVH) and 20 had normal left ventricular mass (HT - LVH), seven normotensive patients with hypertrophic cardiomyopathy (HCM) and a normotensive control group (n = 7). Noradrenaline was measured in arterial and coronary venous plasma using high-performance liquid chromatography. Coronary blood flow was quantified using the gas chromatographic argon method. Indices of left ventricular mass were calculated from the end-diastolic thicknesses of the interventricular septum and the posterior wall determined by echocardiography., Results: The coronary venous plasma concentration of noradrenaline was significantly higher in HT - LVH, HT + LVH and HCM than it was in normotensives. Whereas in normotensives there was a net uptake of noradrenaline (17 +/- 10 pmol/min) across the coronary circulation, a net release of noradrenaline was observed in HT - LVH (69 +/- 26 pmol/min), in HT + LVH (121 +/- 55 pmol/min) and in HCM (341 +/- 96 pmol/min). In a multivariate linear regression analysis model, left ventricular mass correlated significantly with the net noradrenaline release rate (r = 0.64, P < 0.001), whereas arterial blood pressure as an additional independent variable did not correlate with left ventricular mass., Conclusion: The present data demonstrate that an increased left ventricular mass in normotensive and in hypertensive patients is closely coupled to an increased cardiac sympathetic activity, supporting the need for additional studies to determine whether adjunctive sympatholytic therapy is beneficial in patients with left ventricular hypertrophy and increased cardiac noradrenaline release.

Left ventricular hypertrophy in arterial hypertension is characterized by myocyte hypertrophy, myocardial fibrosis, and structural changes of the intramural coronary arteries. Hypertensives with or without left ventricular hypertrophy have a reduced coronary vasodilator reserve due to alterations of the coronary microcirculation. The impairment in coronary vasodilator reserve is likely to initiate a process of malperfusion and malnutrition concomitant with increased metabolic demands. Further, malperfusion is supported by an increase in diastolic filling pressure, which will enhance the extravascular component of coronary resistance. The sum of interactions of these structural alterations of myocardium, interstitium, and coronary vasculature are likely to initiate and maintain a process of myocardial malperfusion and malnutrition, which can provoke functional depression of the myocardial performance, a loss of contractile proteins, an increase in interstitial fibrosis, and, not least, an overall decrease in contractile function in long-standing cardiac hypertrophy. Finally, the reversal of these processes by adequate antihypertensive treatment may contribute to renormalization of cardiac function and to prevention of late cardiac failure in hypertensive heart disease.

Hypertensive left ventricular hypertrophy comprises not only myocyte hypertrophy, but is often associated with interstitial fibrosis and structural alterations of the coronary microcirculation. The consequences are early diastolic dysfunction and often later systolic dysfunction of the left ventricle, resulting in congestive heart failure. Involvement of the coronary resistance vessels leads to an impairment of coronary flow reserve despite normal epicardial arteries. Therefore, antihypertensive treatment should aim at reversing myocyte hypertrophy, restoring myocardial structure, and improvement in coronary flow reserve apart from blood pressure lowering. Many clinical studies have shown that calcium antagonists are effective in lowering blood pressure and can induce regression of left ventricular hypertrophy. Moreover, experimental studies have shown a restoration of myocardial structure. Recent clinical studies have demonstrated a marked improvement of the impaired coronary vasodilator reserve in hypertensive patients after long-term treatment with calcium antagonists. In summary, calcium antagonists can be regarded as an antihypertensive treatment modality that is able to restore myocardial structure and to repair coronary microcirculation and therefore can be considered as causative treatment of hypertensive cardiac remodeling.

Impairment of coronary flow reserve in arterial hypertension and hypertrophy is caused by multiple mechanisms. Medial wall thickening of the small intramural arteries and rarification of capillarization are the major structural alterations in hypertensive hypertrophy. Since the small intramural resistance arteries contribute more to coronary resistance than capillaries, medial wall thickening of the intramyocardial arterioles has to be considered the most relevant mechanism for causing impaired coronary flow reserve in arterial hypertension. Additionally, qualitative changes in myocardial tissue composition and structure, such as reactive interstitial fibrosis, rather than the mere augmentation of the myocardial muscle mass, impair flow reserve extravascularly. Except for the structural vascular and myocardial changes, in some hypertensive patients an impaired endothelium-mediated vasodilation of the microvessels occurs. Preliminary clinical data indicate that myocardial interstitial collagen content can be regressed in some hypertensive patients by clinical antihypertensive therapy over a period of 9-12 months.

Antihypertensive Long-term Therapy with Isradipine/Improvement of coronary flow reserve in patients with arterial and microvascular angina In patients with arterial hypertension coronary flow reserve is often impaired due to left ventricular (LV) hypertrophy and alterations of the coronary microcirculation. Experimental and clinical studies have shown that calcium channel blockers can induce regression of myocardial hypertrophy. Objective of the present study was to see whether chronic antihypertensive treatment with calcium channel blockers can improve the diminished coronary reserve in patients with arterial hypertension and microvascular angina pectoris. Fifteen hypertensive patients with microvascular angina (61 +/- 7 years, normal coronary angiogram, mild LV-hypertrophy) were treated with isradipine (CAS 75695-93-1) (5.3 +/- 0.9 mg/d) for 12 +/- 2 months. Before and after therapy (after a washout period of 1 week) coronary flow was quantitatively measured by the gas chromatographic Argon method. Coronary reserve was calculated as the quotient of coronary resistance under baseline conditions and after dipyridamole (0.5 mg/kg i.v.). Under isradipine therapy systolic blood pressure was lowered from 165 +/- 20 to 140 +/- 13 mmHg (p < 0.01) and diastolic blood pressure from 98 +/- 8 to 88 +/- 6 mmHg (p < 0.01). The LV muscle mass index decreased by 10% from 154 +/- 33 to 139 +/- 28 g/m2 (p < 0.05). Baseline coronary blood flow (81 +/- 13 versus 83 +/- 16 ml/min x 100 g, n.s.) was identical before and after therapy. There were also no differences in coronary perfusion pressure, heart rate, myocardial oxygen consumption and arterio-coronary venous oxygen difference before and after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: In hypertensive patients with angina pectoris, the coronary vasodilator reserve is frequently impaired despite a normal coronary angiogram. Experimental data indicate that structural alterations of the intramyocardial coronary vasculature contribute to an increased minimal coronary resistance and a diminished coronary flow reserve., Methods and Results: In 14 patients (10 men and 4 women) with arterial hypertension and 8 normotensive subjects, minimal coronary resistance and vasodilator reserve (dipyridamole: 0.5 mg/kg body wt, gas chromatographic argon method) were determined after the angiographic exclusion of relevant coronary artery disease. Coronary reserve was depressed in hypertensive patients (2.7 +/- 2.3 vs 4.6 +/- 1.3, P < or = .05) due to increased minimal coronary resistance (0.64 +/- 30 vs 0.24 +/- 0.055 mm Hg.min.100 g.mL-1, p < or = 0.002). In right septal biopsies, mean external arteriolar diameter (21.6 +/- 2.3 vs 17.2 +/- 2.5 microns, P < or = .001), mean arteriolar wall area (271 +/- 61 vs 172 +/- 62 microns 2, P < or = .01), percent medial wall area (69.9 +/- 4.0 vs 66.0 +/- 3.2%W, P < or = .05), mean periarteriolar fibrosis area (216 +/- 122 vs 104 +/- 68 microns 2, P < or = .05), and volume density of total interstitial fibrosis (3.6 +/- 1.8 vs 1.9 +/- 0.5Vv% fibrosis, P < or = .05) were increased in hypertensive patients compared with normotensive subjects. Minimal coronary resistance correlated with %W (r = .6, P < or = .003) and Vv% fibrosis (r = .62, P < or = .002). Left ventricular mass index (111 +/- 21 vs 97 +/- 17 g/m2, P = NS) and left ventricular end-diastolic pressure (12 +/- 6 vs 8 +/- 3 mm Hg, P = NS) did not correlate significantly with minimal coronary resistance. In multivariate analysis, both %W and Vv% fibrosis explained half of the variability of minimal coronary resistance (r2 = .5, P < or = .002)., Conclusions: Structural remodeling of the intramyocardial coronary arterioles and the accumulation of fibrillar collagen are decisive factors for a reduced coronary dilatory capacity in patients with arterial hypertension and angina pectoris in the absence of relevant coronary artery stenoses.

Objective: To evaluate the relationship between the ankle/arm blood pressure index (AAI, the ratio of ankle to arm systolic blood pressure, a measure of peripheral arterial disease) and short-term cardiovascular morbidity and mortality in older adults with systolic hypertension., Design: Prospective cohort study, 1- to 2-year follow-up (mean, 16 months)., Setting: Eleven of 16 field centers from the Systolic Hypertension in the Elderly Program., Participants: 1537 older men and women with systolic hypertension., Main Outcome Measures: All-cause mortality, coronary heart disease (CHD) mortality, cardiovascular disease (CVD) mortality, and CHD and CVD morbidity and mortality., Results: The AAI was measured at the 1989-1990 clinic examination and was 0.9 or less in 25.5% of 1537 participants. A low AAI was associated with most major CHD and CVD risk factors. In those with a low AAI (< or = 0.9) compared with those with an AAI of more than 0.9, age- and sex-adjusted relative risks for mortality end points at follow-up were as follows: total mortality, 3.8 (95% confidence interval [CI], 2.1 to 6.9); CHD mortality, 3.24 (95% CI, 1.4 to 7.5); and CVD mortality, 3.7 (95% CI, 1.8 to 7.7). For CVD morbidity and mortality, the age- and sex-adjusted relative risk was 2.5 (95% CI, 1.5 to 4.3). After adjustment for baseline CVD and other cardiovascular risk factors, the relative risk for total mortality was 4.1 (95% CI, 2.0 to 8.3) and for CVD morbidity and mortality, 2.4 (95% CI, 1.3 to 4.4). Results were similar when participants with clinical CVD at baseline were excluded., Conclusion: A low AAI appears to be an important predictor of morbidity and mortality among older adults with systolic hypertension.

Individuals with hypertension and electrocardiographic (ECG) evidence of left ventricular hypertrophy (LVH) have a 10-fold greater risk of developing cardiac failure than hypertensives without ECG evidence of LVH. LVH in hypertension is characterized by myocardial fibrosis and structural changes to the small intramural arteries. Hypertensives with or without LVH have reduced coronary vasodilator reserve due to hypertensive disease of small coronary arteries. Prognosis of arterial hypertension is largely determined by cardiac complications. The aim of treatment of hypertensive heart disease is to reverse myocardial hypertrophy in order to prevent progression to hypertensive heart failure, as well as reversal of the hypertensive disease of small coronary arteries in order to improve coronary reserve. On the development of hypertensive heart failure, administration of digitalis, diuretics and angiotensin converting enzyme (ACE) inhibitors should be initiated. Although regression of LVH can be induced by dihydropyridine calcium channel blockers, ACE inhibitors and sympatholytic substances, clinical evidence of the reversal of hypertensive disease of small coronary arteries has still to be established.

Arterial hypertension leads to left ventricular hypertrophy. In proportion to increased left ventricular systolic pressure, left ventricular hypertrophy is considered to be of adaptive nature from the point of view of wall stress regulation. In the beginning, left ventricular function is normal, whereas diastolic filling is already compromised by the process of hypertrophy and altered ventricular geometry. In case of ventricular dilation and wall thinning, wall stress increases and leads to an increment in myocardial oxygen demand and a decrease of left ventricular ejection fraction. This is followed by a further decline in intrinsic myocardial contractility and a decrease in the elastic material properties of the myocardium. The structure of the myocardium is characterized by myocyte hypertrophy, a process of reactive and reparative fibrosis and alterations of the coronary microcirculation. Coronary vasodilator reserve is markedly impaired and is likely to initiate a process of malperfusion and malnutrition under increased metabolic demands. Particularly, the combined involvement of myocytes, interstitium, and intramyocardial vasculature appears to predispose to late heart failure after prolonged exposure to chronic pressure overload in arterial hypertension.

The coronary microcirculation was investigated by the argon gas method in ten patients (eight men, two women; mean age 56 [44-63] years) before and after an average of 12.9 (9-18) months of treatment with the cardioselective beta-receptor blocker bisoprolol. Left ventricular muscle mass was measured echocardiographically, before and after the treatment. All these patients were known to have hypertension, with exercise-related angina and ischaemic signs in the resting ECG, but normal coronary angiograms. After the treatment period both maximal coronary perfusion and coronary reserve had increased by 22%. At the same time, left ventricular muscle mass had decreased from 161 +/- 18 to 146 +/- 21 g/m2. These results demonstrate that blood pressure reducing treatment can bring about not only a regression of left ventricular hypertrophy, but also an improvement in coronary reserve.

Arterial hypertension is the most frequent cause of a disturbance of coronary microcirculation. Inspite of having normal epicardial coronary arteries, patients with arterial hypertension often have symptoms of angina pectoris and a positive exercise tolerance test. The angina pectoris-symptoms in patients with arterial hypertension are due to functional and structural alterations of the coronary microcirculation. Consequently, an antihypertensive therapy should not only aim at lowering blood pressure and reversing myocardial hypertrophy, but also improve coronary microcirculation in order to avoid the consequences of chronic ischemia on the myocardium. Until now, only experimental studies have indicated that antihypertensive therapy can improve coronary flow reserve. To determine to what extent under clinical conditions coronary flow reserve can be improved, in hypertensive patients maximal coronary blood flow, minimal coronary resistance, and coronary reserve (Dipyridamol) were studied before and after a long-term antihypertensive treatment (9-12 months) with the ACE-inhibitor enalapril (10-20 mg/d). To assess the chronic effects rather than the acute effects of the antihypertensive pharmacon, the coronary microcirculation was studied after intermission of medical therapy for a period of 1 week. Along with a decrease in LV muscle mass by about 8%, coronary reserve was improved after enalapril by 48%. It is likely that the observed increase in coronary reserve is related to the reversal of structural vascular abnormalities at the level of the coronary microcirculation. Consequently, it seems that reparation of hypertensive remodeling of the coronary microcirculation can be induced by ACE-inhibitor therapy.

In arterial hypertension left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations of the coronary microcirculation. This leads to an impairment of diastolic function of the left ventricle and coronary flow reserve despite normal epicardial arteries. Consequently, antihypertensive treatment should aim at [13] reversing myocyte hypertrophy, [14] restoring myocardial structure and [8] improving coronary flow reserve along with blood pressure normalization.

Unlabelled: Hypertension, especially if associated with left ventricular hypertrophy (LVH), is a risk factor in complex ventricular arrhythmia (VA) and sudden cardiac death (SCD). To determine the effectiveness of the clinical use of programmed ventricular stimulation (PVS) we studied 40 symptomatic hypertensive patients after excluding coronary heart disease (CHD), as characterized by dizziness and palpitation, syncope, aborted SCD and/or documented complex VA. PVS revealed a normal result, i.e. a maximum of six ventricular echobeats, in 70% (group A) and a pathological result, i.e. ventricular tachycardia (VT) or fibrillation (VF) in 30% (group B). Both groups differed significantly with respect to LV (left ventricular) muscle mass: 158 +/- 45 (A) vs. 222 +/- 112 (B) g.m-2, LVEF (left ventricular ejection fraction): 71 +/- 17% (A) vs. 47 +/- 18% (B) and LV end-systolic volume index: 34 +/- 25 (A) vs. 63 +/- 27 (B) ml.m-2. Coronary reserve was comparably reduced in both groups: 2.6 +/- 1.0 (A) vs. 2.3 +/- 0.6 (B). In 3/8 (37%) patients with aborted SCD and VT/VF the clinical VA (2/2 VT and 1/6 VF) could be induced, whereas in the remaining five patients nsVT or no complex VA was induced. The therapeutic regimen included no drugs in 30%, beta-blockers in 50%, serial drug testing in 12% and implantation of an automatic cardioverter defibrillator (AICD) in 8% of patients. Ventricular late potentials (LPs), detected by the signal averaging electrocardiogram, represent zones of delayed myocardial activation, which may become an origin of ventricular tachycardias. Three criteria constitute a positive LP: (1) QRS duration greater than 114 ms, (2) root mean square voltage of the last 40 ms less than 20 microV and (3) duration of low amplitude signal below 40 microV greater than 38 ms. To look for the prognostic value of LP in hypertension we investigated 43 hypertensive patients without evidence of CHD. All three criteria were positive in 4/43 patients (9%), three of them demonstrating inducible monomorphic VT during PVS. 17/30 patients (56%) with LVH had at least one positive criterion, whereas only one out of 13 patients without left ventricular hypertrophy (8%) had one positive criterion. Symptomatic patients presenting with syncope, aborted SCD or documented VT/VF differed significantly from patients without symptoms or complex arrhythmias in regard to all three criteria., Conclusion: In hypertensive heart disease clinical arrhythmias as well as the result of electrophysiological testing are closely related to left ventricular performance and hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypertensive left ventricular hypertrophy comprises myocyte hypertrophy, interstitial fibrosis and structural alterations in the coronary microcirculation. This leads to impairment of diastolic function in the left ventricle and coronary flow reserve despite normal epicardial arteries. Consequently, antihypertensive treatment should aim at (1) reversing myocyte hypertrophy, (2) restoring myocardial structure and (3) improving coronary flow reserve without lowering blood pressure. In recent years many clinical studies have shown that regression of hypertensive hypertrophy can be induced by long-term treatment with ACE inhibitors, calcium-channel blockers, beta-receptor blockers and antisympathonic drugs. However, vasodilators and diuretics, which stimulate adrenoceptor activity and increase angiotensin II levels, were found to be less effective in reversing left ventricular hypertrophy. The trophic influence of catecholamines and angiotensin II on the myocardium counteracts the effect of systolic wall stress reduction due to blood pressure lowering. As regards reversal of interstitial fibrosis, ACE inhibitors seem to be effective, because fibroblast growth was found to be stimulated by angiotensin II. Recently, clinical studies have confirmed previous experimental data that improvement in impaired coronary vasodilator reserve can be realized by long-term antihypertensive therapy. In adopting an antihypertensive treatment strategy prime consideration should be given to reversal of cardiac remodelling through restoration of myocardial structure and repair of the coronary microcirculation.

In 53 patients with a history of arterial hypertension and 16 normotensive control subjects, coronary blood flow reserve by means of the argon method, and peripheral vascular flow reserve by means of venous occlusion plethysmography, were studied. The coronary flow reserve, expressed as the ratio of coronary vascular resistance under resting conditions to the minimal coronary vascular resistance after the administration of dipyridamole, was 4.34 +/- 0.89 in the normotensive group and 2.18 +/- 0.60 in the hypertensive group. There was no significant difference in forearm peak flow after 3 min of arterial occlusion between normotensive and hypertensive patients, while the peripheral minimal vascular resistance was significantly higher in hypertensive patients (8.8 +/- 3.8 mmHg x ml.min-1 x 100 ml-1 tissue) as compared to normotensive subjects (6.37 +/- 2.37 mmHg x ml.min-1 x 100 ml-1 tissue). Parallel to the reduction in coronary reserve, the peripheral flow reserve, expressed as the ratio of peripheral resting vascular resistance to peripheral minimal vascular resistance after 3 min of arterial occlusion, was significantly lower (P less than 0.01) in hypertensive subjects (3.85 +/- 2.28) as compared to normotensive subjects (5.31 +/- 1.72). These data suggest that in hypertensives an impaired vasodilator reserve of both coronary and peripheral microcirculation exists.

Cardiac constituents affected in arterial hypertension comprise the myocardium, interstitium and coronary circulation. With regard to coronary circulation, arterial hypertension is an important risk factor in coronary artery disease, but even in the absence of coronary artery disease, hypertensive patients frequently have angina pectoris or reveal electrocardiographic abnormalities suggestive of myocardial ischaemia due to coronary insufficiency. Under clinical conditions, determination of coronary flow reserve (dipyridamole; Argon-method) allows for the evaluation of impairment of coronary regulatory reserve. In comparison to healthy normotensives, coronary haemodynamics in hypertensive patients with microvascular angina are characterized by a severely increased minimal coronary resistance and reduced maximal coronary blood flow to dipyridamole. Accordingly, coronary reserve is markedly reduced by about 40%, and metabolic, myocardial and vascular factors may be involved in this reduction. In the compensated stage of arterial hypertension, with concentric left ventricular hypertrophy, myocardial factors, such as myocyte hypertrophy, extravascular compressing forces and functional implications of impaired relaxation, as well as metabolic factors, contribute to impairment in coronary reserve to a minor extent. The reduction in coronary flow reserve is not proportional to the elevation in left ventricular muscle mass and thus the degree of left ventricular hypertrophy does not seem to determine the reduction in vasodilator reserve directly. Thus the reduction in coronary reserve seems to be primarily the consequence of an impaired vasodilating capacity of the coronary resistance vessels, as indicated by a severely increased minimum coronary resistance to dipyridamole, i.e. a severely reduced overall coronary conductance capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial hypertension is the most frequent cause of a disturbance of coronary microcirculation. Inspite of having normal epicardial coronary arteries, patients with arterial hypertension often have symptoms of angina pectoris and a positive exercise tolerance test. The angina pectoris symptoms in patients with arterial hypertension are due to functional and structural alterations of the coronary microcirculation. Consequently, an antihypertensive therapy should not only aim at lowering blood pressure and reversing myocardial hypertrophy, but also to improve coronary microcirculation in order to avoid the consequences of chronic ischemia on the myocardium. Until now, only experimental studies have indicated that antihypertensive therapy can improve coronary flow reserve. To determine (also under clinical conditions) if coronary flow reserve can be improved, in 30 hypertensive patients maximal coronary blood flow, minimal coronary resistance, and coronary reserve (dipyridamol) were studied before and after a long-term antihypertensive treatment (9-12 months) with an ACE-inhibitor (enalapril 10-20 mg/d), a calcium channel blocker (diltiazem 120-180 mg/d) and a beta 1-selective beta-receptor-blocker (bisoprolol 5-10 mg/d). To assess the chronic effects rather than the acute effects of the antihypertensive pharmacon, coronary microcirculation was studied after intermission of medical therapy for a period of 1 week. Along with a comparable decrease in LV muscle mass, coronary reserve was improved after enalapril by 48%, after diltiazem by 48%, and after bisoprolol by 22%. It is possible that the observed increase in coronary reserve is related to the reversal of structural vascular abnormalities on the level of the coronary microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary hemodynamics (blood flow, coronary reserve, myocardial oxygen consumption) were analyzed in both experimental and clinical hypertension. Significantly reduced coronary reserve was found in hypertensive patients with left ventricular hypertrophy. Medial hypertrophy of small coronary vessels associated with a marked increase in the wall thickness/radius ratio was considered sufficient to explain the impaired coronary flow in hypertensive left ventricular hypertrophy. After long-term pharmacotherapy, there was normalization of both medial hypertrophy and coronary reserve. This small-vessel abnormality correlates well with clinical findings in hypertensive heart disease (angina and electrocardiographic changes despite normal coronary arteriogram). Moreover, this structural adaptation of the small vessels may carry the inherent risk of an impaired oxygen supply to the hypertrophied myocardium. Thus, late cardiac failure of the hypertrophied heart in hypertension may be attributed, in part, to this microcirculation disorder. Conversely, reversal of left ventricular hypertrophy and of hypertrophy of vascular smooth muscle by specific pharmacotherapy can be considered a possible rational approach to the prevention of cardiac failure in hypertensive patients. Controlled clinical trials are needed to confirm these findings with regard to prevention of heart failure, and pharmacotherapeutic studies are necessary to define the optimal drug regimen for reversal of vascular smooth muscle hypertrophy.

Arterial hypertension is the most common cause of congestive heart failure and an important risk factor in coronary artery disease (CAD). However, even in the absence of CAD, coronary reserve is frequently impaired in hypertensive patients. To study whether the reduced coronary reserve is due to the degree of left ventricular hypertrophy (LVH) or is a consequence of primary vascular alterations, coronary reserve was determined in 31 hypertensive patients (age of 56 +/- 10 years; systolic/diastolic blood pressure of 167 +/- 18/98 +/- 9 mm Hg) with angina pectoris and normal coronary angiogram. Coronary reserve was determined by measuring coronary resistance before and after dipyridamole (0.5 mg/kg of body weight i.v.). Coronary blood flow was measured quantitatively by the gas chromatographic argon method. LV muscle mass was measured by ventriculography. Twelve normotensive patients (age of 52 +/- 8 years) were studied for comparison. Coronary resistance was 20% higher in hypertensive than in normotensive patients, whereas coronary blood flow at rest was not significantly different. The maximal coronary blood flow after dipyridamole was 40% lower in hypertensive than in normotensive patients; accordingly, minimal coronary resistance was significantly increased by 112% in hypertensive patients (p less than 0.0005). Coronary reserve was reduced by 37% (p less than 0.001) in hypertensive patients compared with normotensive patients. Between the impairment in coronary reserve and left ventricular muscle mass, no significant correlation (r = 0.024, n.s.) was found. The impaired coronary vasodilator reserve is reflected by episodes of transient myocardial ischemia during ST-segment monitoring.

The cardiac organ manifestation of arterial hypertension comprises the myocardium itself with left-ventricular hypertrophy, the interstitium with perivascular and interstitial fibrosis, and the coronary circulation with disease of large and small coronary arteries. The consequences of the sum and interactions of these cardiac organ manifestations have an impact on left-ventricular systolic and diastolic function, the ischemic risk, and the occurrence of arrhythmias in hypertensive patients. As the prognosis of arterial hypertension is determined, to a considerable extent, by these cardiac complications, the aim of treatment of hypertensive heart disease is reversal of the myocardial hypertrophy in order to prevent later progression to hypertensive failure. A further goal of therapy is reversal of hypertensive coronary microangiopathy in order to improve the coronary reserve and to reduce the ischemic risk. Regression of hypertrophy can be induced by suitable antihypertensive drugs (calcium channel blockers of the dihydropyridine type, ACE inhibitors, and sympatholytic substances). While normal systolic function was maintained in the compensated stage of hypertensive hypertrophy and was not significantly influenced by antihypertensive therapy, diastolic function was impaired in a very early stage of arterial hypertension. Both the phase of isovolumic relaxation and the phase of early diastolic filling were imparied, while after long-term antihypertensive treatment with Ca-channel blockers of the dihydropyridine type or ACE inhibitors, only the latter one was improved. From preliminary results there is clinical evidence that hypertensive disease of small coronary arteries can be reversed after long-term antihypertensive treatment with a consequently improved coronary reserve and a reduced ischemic risk. Moreover, to what extent the prognosis of hypertensive heart disease can be improved by reversal of myocardial hypertrophy and disease of small coronary arteries is yet unknown.

The influence of blood fluidity on coronary reserve in patients with essential hypertension and normal coronary arteries was examined. The coronary reserve, expressed as the ratio of coronary vascular resistance under resting conditions to the coronary vascular resistance after administration of dipyridamole, was 4.1 +/- 1.5 in 10 normotensive patients with normal coronary arteries, whereas the mean value was only 2.4 +/- 0.8 in 35 hypertensive patients. When compared with the normotensive control group the 35 hypertensive patients had significantly higher levels of hematocrit (45.9 +/- 3.7 vs 42.3 +/- 3.6; p less than or equal to 0.01) and plasma viscosity (1.39 +/- 0.07 vs 1.32 +/- 0.06 mPas; p less than 0.01). Plasma fibrinogen (291 +/- 67 vs 251 +/- 25 mg/dl) and whole blood viscosity at a shear rate of 2 s-1 (7.77 +/- 1.1 vs 7.21 +/- 1.28 mPas) and at a high shear rate of 100 s-1 (4.23 +/- 0.57 vs 3.91 +/- 0.64 mPas) demonstrated a trend without statistical significance toward higher values in hypertensive patients. When the hypertensive group was further divided according to the coronary reserve (less than 2.5, severely impaired coronary reserve; greater than 2.5 less than 3.8, moderately impaired coronary reserve), the parameters of blood fluidity clearly correlated inversely with coronary reserve. This suggests a major importance of rheologic abnormalities on impaired coronary reserve in hypertensive patients.

Arterial hypertension is associated with an increased cardiovascular mortality and an increased risk of sudden cardiac death. Therefore, the prevalence of ventricular arrhythmias, identified on 24-hour ambulatory electrocardiographic monitoring, was analyzed in 54 patients (aged 56 +/- 10 years) with arterial hypertension and normal coronary angiograms with respect to left ventricular muscle mass, mass-to-volume ratio, systolic wall stress and coronary microangiopathy. Ventricular ectopic beats (VEBs) were assessed according to a score (modified Lown classification: 1 = no VEB, 2 = less than 30 VEB/hour, 3 = greater than 30 VEB/hour, 4 = polymorphic VEB, 5 = bigeminys, 6 = couplets, 7 = nonsustained ventricular tachycardia). Coronary blood flow was measured by the gas chromatographic argon method. Coronary reserve was determined by measuring coronary resistance before (Rcor) and after (Rmin) administration of intravenous dipyridamole (0.5 mg/kg body weight) (Cor Res = Rcor/Rmin). The frequency (p less than 0.05) and severity (p less than 0.025) of VEBs was higher in normotensive than in hypertensive patients. Although the score of VEBs did not correlate with left ventricular muscle mass (r = 0.20, difference not significant), a slight correlation with mass-to-volume ratio (r = 0.32; p less than 0.05) and systolic wall stress (r = 0.30; p less than 0.05) was found. Hypertensives with a severely reduced Cor Res (less than 2.0) had a significantly higher score of VEBs than those with a nearly normal Cor Res (greater than 3.0) (5.0 +/- 1.5 vs 3.5 +/- 1.7; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

In previous studies swimming training (ST) of spontaneously hypertensive rats (SHR) at 36 degrees water temperature (WT) led to a decrease in blood pressure (BP). A similar effect of ST has not been described in human hypertension. Our purpose was to investigate the influence of WT on this training effect, the influence of ST on LV hypertrophy and the involvement of adrenergic stimuli in the latter. Male SHR (20 weeks old) were divided randomly into 4 groups. 1) SHR sedentary 2) SHR ST 36 degrees 3) SHR ST 26 degrees 4) SHR ST 36 degrees + atenolol (50 mg/kg/die). ST was performed 2 X 90 min/day for 31 days and then reduced to 2 X 60 min/day. After 7 weeks of ST BP was lower in all ST groups compared with SHR sedentary (p less than 0.001). BP was higher in ST 26 degrees than in ST 36 degrees (p less than 0.05). No additional effect of atenolol on BP was observed. The increase in the degree of LV hypertrophy during ST (ST 36 degrees: +15%; ST 26 degrees: +26%) could be prevented by atenolol (ST 36 degrees + atenolol: -1.5%). ST 36 degrees led to improved ventricular and myocardial performance with decreased LV wall stress ("luxury hypertrophy"), while in ST 26 degrees ventricular dilatation occurred with increased systolic wall stress and elevated LVEDP. It was uncertain whether this should be interpreted as a state of LV pre-insufficiency in ST 26 degrees in spite of no indications of impaired myocardial contractile capability. Peripheral vascular resistance (PVR) was significantly reduced by ST. The reduction was more evident in ST 26 degrees, but was partially compensated for by an increased cardiac output. The weights of adrenal glands increased (p less than 0.001), most markedly for ST 26 degrees. The level of thyroid hormones (T3 and fT3) was increased in ST 26 degrees. In summary, ST proved to be effective in lowering BP of SHR. WT had great influence with respect to cardiovascular adaptation and mechanisms involved in ST of SHR. Cardioadrenergic drive was of great significance for the process of hypertrophy during ST in SHR.

The purpose of the present study was to determine whether an antihypertensive treatment with the dihydropyridine nitrendipine can induce regression of severe hypertensive hypertrophy and, whether alterations in systolic and diastolic ventricular function do occur. Eleven patients (age 49 +/- 11 years) with hypertensive hypertrophy were treated with nitrendipine (10-40 mg/day) for 12 months. Before and after therapy left ventricular hypertrophy, systolic, and diastolic function were measured by M-mode, two-dimensional- and digitized M-mode echocardiography. Systolic blood pressure dropped from 185.5 +/- 19.8 to 164.1 +/- 15.6 mm Hg (p less than 0.05). Left ventricular muscle mass was reduced from 234.5 +/- 51.2 to 201.5 +/- 37.9 g/m2 (p less than 0.05). Systolic wall stress (257.2 +/- 50.5 vs 245.2 +/- 44.4 x 10(3) dyn/cm2) and fractional shortening (34.9 +/- 6.1 vs 37.1 +/- 5.4%) remained nearly unchanged. The peak rate of left ventricular internal dimension change during diastole (MLVD), as an index of rapid early diastolic filling was increased (13.1 +/- 3.0 vs 16.5 +/- 3.7 cm/s; p less than 0.01), the relaxation time index, as an index of isovolumic relaxation, remained nearly unchanged (76 +/- 35 vs 64 +/- 24 ms; n.s.). A long-term treatment with nitrendipine regressed hypertensive left ventricular hypertrophy in proportion to blood pressure reduction. While systolic function remained unchanged as a consequence of an unaltered systolic wall stress, i.e. afterload, diastolic filling was markedly improved due to changes in left ventricular geometry through reduction in mass to volume ratio. Since relaxation time index remained nearly unchanged, factors contributing to the phase of isovolumic relaxation were not essentially affected by regression of left ventricular hypertrophy.

The hypertensive damage to the target organ "heart" comprises the sum and interactions of the cardiac organ manifestations of arterial hypertension such as myocardial hypertrophy and disease of large and small coronary arteries. As the prognosis of arterial hypertension is determined, to a considerable extent, by these cardiac complications, the aim of treatment of hypertensive heart disease is reversal of the myocardial hypertrophy in order to prevent later progression to hypertensive failure. A further goal of therapy is reversal of hypertensive small coronary disease in order to improve the coronary reserve. While the evidence that regression of hypertrophy can be induced by suitable antihypertensive drugs (calcium channel blockers of the dihydropyridine type, ACE inhibitors, and sympathicolytic substances) is practically conclusive, clinical evidence of reversal of hypertensive small coronary disease has yet to be provided. Moreover, we do not know at present to what extent the prognosis of hypertensive heart disease can be improved by reversal of hypertrophy. Once the stage of hypertensive heart failure is reached, the principles of medical management of heart failure with digitalis, diuretics, and ACE inhibitors apply.

The significance of various factors for the development of structural dilatation in the chronically pressure-loaded and failing heart were evaluated. The investigations were performed on male rats with renal (Goldblatt II) and spontaneous (Aoki-Okamoto) hypertension at different stages of haemodynamic overload. Two groups of SHR were submitted to intermittent feeding (SHR IF); one group received additionally the beta-blocking agent atenolol (50 mg/kg b.w.; SHR IF + beta Bl.). Haemodynamic measurements were carried out under open chest conditions. Myosin isoenzyme pattern, hydroxyproline concentration and circulating blood volume were determined. Transformation to slower myocardium per se, induced by IF, did not lead to significant change in ventricular configuration. After additional blockade of beta-adrenergic receptors there were indications of unfavourable development of left ventricular configuration. Inhibition of hypertrophic mass increase due to curtailed adrenergic stimulation could be an influential factor in the development of dilatation. Further investigations, however, are required to establish the relationship between the adrenergic system, on the one hand, and degree of hypertrophy as well as structural dilatation of the ventricle, on the other hand. The established marked increase in hydroxyproline concentration of the dilated ventricle of SHR in congestive failure is consistent with the assumption of a causal link between the degree of fibrosis and structural dilatation. Observations on rats with aorto-caval shunt and Goldblatt II rats with eccentric hypertrophy and corresponding increase in filling potential or circulating blood volume indicate a correlation between the latter and ventricular size. Thus, we assume that curtailed protein synthesis, fibrosis and regulatory processes related to water and electrolyte balance, but not myocardial transformation per se, play a role in the development of structural dilatation. The relative contribution of each factor, however, may depend on the experimental model that is used.