Angiotensin I converting enzyme activity in hypertension. Relationship to blood pressure, renin-sodium profiles, and antihypertensive therapy

The activity of the angiotensin I converting enzyme was measured in 55 patients with untreated essential hypertension, 11 patients with untreated renovascular hypertension, five patients with untreated primary aldosteronism, and 23 normotensive subjects. Converting enzyme activity was significantly higher (p less than 0.025 or less) in essential hypertension (28 +/- 1 units/ml) and renovascular hypertension (28.5 +/- 3 units/ml) when compared with the activity in the normotensive subjects (21 +/- 1.5 units/ml). Seventeen (31 percent) of the patients with essential hypertension and three (27 percent) patients with renovascular hypertension had an elevated converting enzyme activity above the mean +2 standard deviations value of the normotensive subjects (32.8 units/ml), ranging from 33 to 55.8 units/ml. Converting enzyme activity was similar in black and white patients and in male and female patients, but it tended to decrease with increasing age in both the hypertensive and the normotensive subjects. In the untreated patients with essential hypertension (n = 55), converting enzyme activity was inversely related to mean arterial pressure and age (r = -0.34, p less than 0.01) and positively related to plasma renin activity (r = 0.31, p less than 0.05). Converting enzyme activity was always decreased during captopril therapy, and it was not affected by beta blockers, but it was increased by diuretics. These findings indicate that converting enzyme activity is elevated in patients with essential and renovascular hypertension.     

Changes in extracellular matrix in subcutaneous small resistance arteries of patients with primary aldosteronism

CONTEXT AND OBJECTIVE: It has been previously demonstrated that aldosterone may possess a strong profibrotic action in vitro and in animal models of genetic or experimental hypertension. Our aim was to evaluate whether such a profibrotic action is present also in the human microcirculation. DESIGN AND PATIENTS: We investigated 13 patients with primary aldosteronism, seven patients with essential hypertension, and 10 normotensive controls. All subjects were submitted to a biopsy of gluteal sc fat tissue. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media to internal lumen ratio was measured. MAIN OUTCOME MEASURES: The total collagen content within the tunica media was detected (Sirius red staining and image analysis), and collagen subtypes were evaluated using polarized light microscopy; under this condition thicker type I collagen fibers appear orange or red, whereas thinner type III collagen fibers are yellow or green. RESULTS: Tunica media to internal lumen ratio was significantly increased in primary aldosteronism and in essential hypertension compared with normotensive controls. Clinic blood pressure values were similar in primary aldosteronism and in essential hypertension, and greater than in normotensive controls. Normotensive controls had less total and type III collagen (3.23 +/- 0.58 and 1.60 +/- 0.22%, respectively) in respect to the two hypertensive groups (P < 0.001). Total collagen and type III vascular collagen were significantly greater in primary aldosteronism (total collagen, 8.17 +/- 1.38%; type III collagen, 6.06 +/- 0.74%; P < 0.05) than in essential hypertension (total collagen, 6.84 +/- 1.15%; type III collagen, 5.25 +/- 0.80%). CONCLUSIONS: Our results indicate that, in small resistance arteries of patients with primary aldosteronism, a pronounced fibrosis may be detected, even more evident than in blood-pressure-matched patients with essential hypertension.     

Role of aldosterone in left ventricular hypertrophy in hypertension

BACKGROUND: Aldosterone induces cardiac fibrosis in experimental animal models, but only limited information is available on the association between aldosterone and left ventricular (LV) hypertrophy in human beings. The aim of the present study was to determine the role of aldosterone in LV geometry and to investigate other types of target organ damage in hypertensive patients. METHODS: A total of 25 patients with primary aldosteronism caused by Conn's adenoma, 29 patients with renovascular hypertension, and 29 patients with essential hypertension (EHT) were included in the present study. Echocardiographic examinations and 24-h ambulatory blood pressure (BP) monitoring were conducted in all subjects. RESULTS: The mean 24-h systolic and diastolic BP in primary aldosteronism and renovascular hypertension were found to be comparable to those in EHT. However, LV mass index adjusted by age, sex, mean 24-h systolic BP, mean 24-h pulse rate, body mass index, and duration of hypertension was significantly increased in the patients with primary aldosteronism and renovascular hypertension compared with values in patients with EHT (150.2 +/- 7.7, 142.3 +/- 7.2, and 115.2 +/- 7.2 g/m(2), respectively). Hypertensive organ damages, such as proteinuria and hypertensive retinopathy, were more pronounced in the patients with renovascular hypertension; however, LV hypertrophy was especially exaggerated in patients with primary aldosteronism. CONCLUSIONS: These results indicate that aldosterone may induce LV hypertrophy in human beings as well as in experimental animals, and that angiotensin II and aldosterone may differentially participate in causing hypertensive target organ damage.     

Hormonal and renal effects of atrial natriuretic peptide in patients with secondary hypertension

To investigate the involvement of atrial natriuretic peptide (ANP) in secondary hypertension, we examined hormonal and renal responses to ANP infusion (0.025 microgram/kg/min) in 27 patients with renal parenchymal hypertension, 10 with primary aldosteronism, 8 with renovascular hypertension, and 15 normotensive subjects. The preinfusion plasma concentration of ANP was significantly higher in patients with renal parenchymal hypertension (120 pg/ml, p less than 0.01) and in patients with primary aldosteronism (98 pg/ml, p less than 0.05) than in the normotensive subjects (40 pg/ml), but it was not greater than in the patients with renovascular hypertension (73 pg/ml, NS). In the patients with renal parenchymal hypertension, plasma ANP correlated negatively with creatinine clearance (r = -0.76, p less than 0.001). Mean blood pressure (-5%, p less than 0.01) and plasma aldosterone (-40%, p less than 0.001) decreased to a similar degree in the four groups during ANP infusion. However, an increase in urinary sodium excretion caused by ANP was higher in the hypertensive than in the normotensive patients (+250% vs. +70%, p less than 0.01) and correlated positively with mean blood pressure during ANP infusion (r = 0.47, p less than 0.001). The removal of adenomas in the patients with primary aldosteronism significantly lowered both plasma levels of ANP and cyclic guanosine 2',3'-monophosphate and reduced an increase in sodium excretion during ANP infusion, whereas the responses of blood pressure and plasma aldosterone to ANP infusion were not altered by the operation. Thus, these results suggest that elevated ANP secretion and increased natriuretic responses to ANP may modify the blood pressure and body fluid volume status in some types of secondary hypertension.     

Increased intima-media thickness of the common carotid artery in primary aldosteronism in comparison with essential hypertension

BACKGROUND: Aldosterone contributes to the accumulation of collagen fibers and extracellular matrix in arterial wall. The aim of this study was to compare intima-media thickness (IMT) of the common carotid artery and carotid bifurcation in patients with primary aldosteronism, essential hypertension and healthy controls. METHODS: Carotid ultrasound studies were carried out in 33 patients aged 42-72 years with primary aldosteronism, 52 patients with essential hypertension and in 33 normotensive controls. RESULTS: The patients with primary aldosteronism had significantly higher IMT of the common carotid artery than patients with essential hypertension and controls (0.987 +/- 0.152 mm; 0.892 +/- 0.154 mm versus 0.812 +/- 0.124 mm; P < 0.001; P < 0.05). There was also significantly higher IMT of the common carotid in patients with essential hypertension compared to control group (0.892 +/- 0.154 mm versus 0.812 +/- 0.124 mm; P < 0.01). The differences between both hypertensive groups remained statistically significant after adjustment for age and 24-h systolic blood pressure (P = 0.001). The differences of the IMT in the carotid bifurcation were statistically significant only between patients with primary aldosteronism and controls (1.157 +/- 0.243 mm versus 0.994 +/- 0.199 mm; P <0.05). CONCLUSION: Patients with primary aldosteronism have increased common carotid IMT compared to the patients with essential hypertension. This finding could be caused by the deleterious effects of aldosterone excess on the fibrosis and thickening of the arterial wall, mainly in the straight segments of vessels.     

Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism

Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K+, ECG PQ interval duration, plasma renin activity, and aldosterone levels (all P< or =0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7+/-1.8 versus 45.5+/-2.0 g/m(2.7); P=0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVI(s); -12.02+/-5.84% versus 6.06+/-3.08%; P=0.012) and posterior wall (-11.13+/-6.42% versus 8.63+/-9.62%; P=0.012). A regression analysis showed that CVI(s) was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for approximately 36% of CVI(s) variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval.     

Cytosolic free calcium concentration in platelets in patients with renovascular hypertension and primary aldosteronism.

To investigate the role of cytosolic free calcium, [Ca2+]i, in secondary hypertension, the levels in platelets from 14 secondary hypertensives (7 renovascular hypertension, 7 primary aldosteronism) were compared with those from 21 essential hypertensives and 15 normotensives by means of the fluorescent indicator, quin-2. The mean BP was significantly higher in both the secondary hypertensives and essential hypertensives (122 +/- 8 and 124 +/- 12 mmHg) than in the normotensives (89 +/- 10 mmHg). Cytosolic free calcium in platelets was significantly higher in the essential hypertensives, but not in the secondary hypertensives, compared with the normotensives (182 +/- 34, 141 +/- 17, 138 +/- 15 nM respectively). There was no significant difference in platelet [Ca2+]i between renovascular hypertension and aldosteronism (142 +/- 19 versus 139 +/- 16 nM). There was no correlation between platelet [Ca2+]i and plasma renin activity, plasma aldosterone concentration or plasma noradrenaline concentration in the three groups. Thus, the increase in platelet [Ca2+]i seen in essential hypertension was not found in patients with secondary hypertension. Our results suggest that the cytosolic calcium handling of secondary hypertensive patients with renal artery stenosis or primary aldosteronism differs from that of essential hypertensives.     

Hyper-responsiveness to angiotensin II is related to cardiac structural adaptation in hypertensive subjects.

BACKGROUND: Angiotensin II has been found to be a growth stimulating factor for myocardial cells. In humans, angiotensin II infusion causes vasoconstriction in systemic and renal vasculature and leads to aldosterone secretion. Our hypothesis was that hyper-responsiveness to angiotensin II is related to left ventricular mass in human essential hypertension. METHODS AND RESULTS: In 30 normotensive individuals and 30 subjects with mild essential hypertension (white men, mean age 26+/-3 years), the responsiveness to angiotensin II was assessed by measuring changes in mean arterial pressure, renal blood flow, glomerular filtration rate and aldosterone secretion in response to i.v. angiotensin II infusion (0.5 and 3.0 ng/kg per min). The provoked changes to angiotensin II infusion were similar in the normotensive and hypertensive group with the exception of an exaggerated increase in mean arterial pressure in hypertensives (14+/-5 versus 10+/-5 mm Hg, P<0.001 at 3.0 ng/kg per min angiotensin II). The increase in mean arterial pressure was correlated with left ventricular mass in hypertensive subjects (angiotensin II 0.5 ng/kg per min: r = 0.49, P<0.005; angiotensin II 3.0 ng/kg per min: r = 0.35, P<0.05); no such correlation was found in the normotensive group. After taking into account baseline mean arterial pressure and body mass index, the increase in mean arterial pressure to angiotensin II 0.5 ng/kg per min was still correlated with left ventricular mass (partial r = 0.50, P<0.01). Similarly, the change of glomerular filtration rate but not of renal blood flow in response to angiotensin II 0.5 ng/kg per min was correlated with left ventricular mass, (r = 0.42, P<0.02) in the hypertensive group but not in the normotensive one. This relationship remained significant even after taking baseline glomerular filtration rate, mean arterial pressure and body mass index into account (partial r = 0.43, P<0.05). CONCLUSION: Hyper-responsiveness to angiotensin II is related to an increased left ventricular mass in hypertensive subjects independent of blood pressure.     

Structural changes in small resistance arteries and left ventricular geometry in patients with primary and secondary hypertension

OBJECTIVE : To prospectively evaluate the interrelationships between left ventricular (LV) geometry and structural characteristics of the vessel wall in small resistance arteries in patients with consecutive primary and secondary hypertension. METHODS : In 14 patients with phaeochromocytoma, 12 with primary aldosteronism, 25 with renovascular, 25 with essential hypertension and 12 normotensive controls, an echocardiographic study for the measurement of LV mass index and relative wall thickness (RWT) was performed. Morphological characteristics of small resistance arteries (relaxed diameter < 300 microm) were directly evaluated by a micromyographic technique. RESULTS : A total of 25 patients had normal LV mass and geometry, 28 patients had normal RWT (< 0.45) and 23 patients had a RWT >or= 0.45; all normotensive subjects had normal LV mass and geometry. Media to lumen ratio (M/L) in subcutaneous small arteries was greater in hypertensive patients with concentric LV hypertrophy in respect to normotensives (ANOVA P = 0.01) and hypertensives with normal LV geometry (ANOVA P = 0.05). In the whole group of hypertensive patients the correlation coefficient between M/L and LV mass index was 0.33 (P < 0.05); the correlation coefficient between M/L and RWT was 0.46 (P < 0.01) and it was higher in primary aldosteronism (r = 0.67) and renovascular hypertension patients (r = 0.46). CONCLUSIONS : A close relation between morphology of subcutaneous small resistance arteries and LV geometric patterns may be observed in hypertensive patients; this relationship is more evident when the renin-angiotensin-aldosterone system is activated.     

Plasma immunoreactive endothelin in essential hypertension

PURPOSE: Endothelin plays a role in the regulation of vascular tonus. Therefore, it has been hypothesized that increased production or release of endothelin or both may contribute to the pathogenesis of hypertension. To assess any changes in the plasma endothelin concentration in essential hypertension, plasma immunoreactive endothelin concentrations were measured in patients with essential hypertension. PATIENTS AND METHODS: We measured plasma immunoreactive endothelin concentrations in 42 subjects with essential hypertension, 12 subjects with borderline hypertension, and 25 normotensive control subjects. RESULTS: The concentrations were higher in hypertensive patients than in borderline hypertensive patients and normotensive subjects (both p less than 0.05), although values in normotensives and hypertensives overlapped. Reverse-phase high-performance liquid chromatography (HPLC) and radioimmuno-assay showed two components of plasma endothelin, one corresponding to synthetic endothelin-1 (1-21) and the other corresponding to synthetic big endothelin (human, 1-38). The HPLC profile of plasma endothelin of hypertensive patients was the same as that of normotensive subjects. Hypertensives with reduced glomerular filtration rates or increased serum creatinine levels had higher plasma endothelin concentrations than hypertensive patients as a whole (p less than 0.05). Mean blood pressure and serum creatinine levels were correlated to plasma endothelin in the hypertensives. Correlation was negative between glomerular filtration rate and the endothelin level in the hypertensives. CONCLUSION: Plasma endothelin was elevated in many hypertensive patients with severe hypertension or renal involvement. Its major components were endothelin-1 and big endothelin.     

Left ventricular structural characteristics in unilateral renovascular hypertension and primary aldosteronism

To assess the importance of the renin-angiotensin system and plasma volume as determinants of hypertensive left ventricular hypertrophy and its anatomy, patients with unilateral renovascular hypertension and primary aldosteronism were studied by echocardiography. Blood pressure, age and sex were matched as closely as possible. The 19 patients with unilateral renovascular hypertension and the 19 patients with primary aldosteronism were similar in age, sex and blood pressure (168 +/- 19/97 +/- 11 and 163 +/- 17/99 +/- 10 mm Hg, respectively), but plasma volume was increased in the patients with primary aldosteronism. Interventricular septal thickness, left ventricular posterior wall thickness, left ventricular mass index and relative wall thickness did not differ between the 2 groups of patients. There was a significant correlation between the level of systolic blood pressure and either left ventricular mass index (r = 0.34, p less than 0.05) or relative wall thickness (r = 0.58, p less than 0.001) in both groups of patients. Left ventricular end-diastolic dimension index was increased in the patients with primary aldosteronism compared with those with unilateral renovascular hypertension (3.2 +/- 0.4 vs 2.9 +/- 0.3 cm/m2, p less than 0.02). When confined to the patients with systolic pressure greater than or equal to 150 mm Hg, relative wall thickness was significantly increased in the patients with unilateral renovascular hypertension. Patients with primary aldosteronism and unilateral renovascular hypertension of similar blood pressure levels, age and sex have almost identical degrees of left ventricular hypertrophy and anatomy. In contrast, the patients with primary oldosteronism had increased left ventricular dimension index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced response of plasma aldosterone to metoclopramide in essential hypertension

Aldosterone responses to posture and the dopamine antagonist, metoclopramide, were studied in seven normotensive controls and 12 patients with essential hypertension. Both groups had similar basal supine plasma renin activity and aldosterone levels. Aldosterone levels of the hypertensive patients were greater than those of the controls 10 min after assuming an upright posture but indistinguishable at 120 min. Metoclopramide induced a peak fourfold increase above basal aldosterone levels in the hypertensive group as compared to a peak twofold increase observed in the normotensive controls. Mean 120-min integrated aldosterone response area for the hypertensives (237 +/- 44 10(-10) mol min/l) was greater (P less than 0.05) than that for normotensive subjects (106 +/- 32 10(-10) mol min/l). Simultaneous cortisol, plasma renin activity, and serum potassium levels were unaffected by metoclopramide. It is concluded that dopaminergic modulation of aldosterone secretion may be altered in essential hypertension.     

高血压颈动脉内-中膜增厚与血浆内皮素的关系

目的 :探讨高血压颈动脉内 中膜增厚 (IMT)与血浆内皮素 (ET)之间的关系。方法 :多普勒超声诊断仪检测 93例原发性高血压 (EH)患者 (1级高血压 2 9例 ,2级高血压 38例 ,3级高血压 2 6例 )与 32例正常对照者的颈动脉IMT ,放射免疫法检测血浆ET。结果 :与正常对照组比较 ,EH组颈动脉IMT增厚 ,以 2、3级EH患者明显 ,血浆EH升高 ,IMT与ET呈正相关 (r =0 .0 6 9,P <0 .0 1)。结论 :ET可能参与EH颈动脉IMT的发生、发展过程     

Ratio of serum aldosterone to plasma renin concentration in essential hypertension and primary aldosteronism.

The ratio of serum aldosterone to plasma renin activity (PRA) has been proposed as sensitive screening method in the diagnosis of primary aldosteronism under random conditions. However, the method for determination of renin activity is hampered by the necessity of ice cooling during storage and transport. The present study was therefore conducted to examine the ratio of serum aldosterone to plasma renin concentration (ARR) and its usefulness in diagnosis of primary aldosteronism under ambulatory conditions and given antihypertensive medication. 146 patients with arterial hypertension who consecutively attended the outpatient clinic were studied prospectively. Patients with secondary hypertension besides primary aldosteronism were not included in the series. 37 normotensive patients served as control. Also, 17 patients with known primary aldosteronism were retrospectively examined. Among the hypertensive group 2 patients with Conn's syndrome were newly detected (1.4%). ARR was 7.92 +/- 6.04 [pg/ml]/[pg/ml] in normotensive controls (range from 2.03 to 26.98), 14.61 +/- 18.50 [pg/ml]/[pg/ml] in patients with essential hypertension (n = 144, range from 0.41 to 115.45) and 155.92 +/- 127.84 [pg/ml]/[pg/ml] in patients with primary aldosteronism (n = 19, range from 6.75 to 515). 17 of the 19 patients with Conn's syndrome had an ARR of more than 50. Under ongoing drug treatment this represents a sensitivity of 89% and a specificity of 96%. Sensitivity decreased to 84% and specificity increased to 100% when a second criteria (aldosterone > or = 200 pg/ml) was included. In summary, ARR using renin concentration is a useful screening parameter for primary aldosteronism.     

QT interval in patients with primary aldosteronism and low-renin essential hypertension

INTRODUCTION: QT interval prolongation increases the risk of sudden death in several medical conditions. Patients with primary aldosteronism and salt-sensitive hypertension experience more cardiovascular events than those with normal-renin essential hypertension. QT interval prolongation might represent one of the risk factors for cardiovascular events in these patients. The aim of the present study was to evaluate the QT interval in patients with primary aldosteronism and low-renin essential hypertension (LREH). METHODS: Twenty-seven patients with primary aldosteronism, 17 patients with LREH, 117 patients with essential hypertension and 25 healthy individuals were studied. Plasma aldosterone, plasma renin activity, and aldosterone to plasma renin activity ratio (ARR) were determined. Corrected QT intervals (QTcs) were measured from a 12-lead electrocardiogram. RESULTS: The QTc was longer in primary aldosteronism (434 +/- 23 ms) and LREH (430 +/- 18 ms) compared with essential hypertension (419 +/- 22 ms) and healthy controls (412 +/- 19 ms) (P = 0.0004). The prevalence of QTc longer than 440 ms was higher in primary aldosteronism (48%) and LREH (23%) compared with essential hypertension (11%) and healthy controls (4%) (P < 0.0001). QTc correlated with plasma aldosterone (P = 0.01), ARR (P = 0.02), and diastolic blood pressure (P = 0.01). ARR (P = 0.01) and systolic blood pressure (P = 0.01) were identified as independent predictors of QTc. CONCLUSIONS: We postulate that the elevated aldosterone secretion contributes to the prolongation of the QT interval in patients with primary aldosteronism and LREH through both a depletion of intracellular potassium concentration and higher blood pressure values. QTc measurement might represent one simple, non-invasive and reproducible index to characterize the cardiovascular risk in patients with primary aldosteronism and LREH.     

Plasma endothelin levels in hypertension and chronic renal failure

Endothelin-1 is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-1, plasma levels of immunoreactive endothelin-1 were measured in 32 research subjects with normal renal function (21 normal subjects and 11 patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-1 levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-1 levels than normal subjects (2.29 +/- 1.09 vs. 1.41 +/- 0.50 pg/ml, p less than 0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n = 17) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 7) (3.08 +/- 3.43 vs. 0.73 +/- 0.34 pg/ml, p less than 0.05), and the hemodialyzed hypertensive group (n = 18) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 33) (2.66 +/- 1.92 vs. 1.35 +/- 0.73 pg/ml, p less than 0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-1 levels. These data suggest that circulating endothelin-1 may be partly involved in the development or maintenance of hypertension in humans.     

Impact of aldosterone on left ventricular structure and function in young normotensive and mildly hypertensive subjects

Left ventricular (LV) hypertrophy is an independent risk factor for cardiovascular morbidity and mortality. Experimental data revealed that elevated circulating aldosterone is associated with increased collagen accumulation resulting in myocardial fibrosis. To analyze whether aldosterone is also associated with cardiac structural and functional changes in humans, we examined the effects of aldosterone on LV structure and function before and after suppression of aldosterone by increasing oral salt intake. The study group comprised 26 normotensive male white healthy control subjects (age 26 +/- 3 years) and 31 male white subjects (age 25 +/- 3 years) with mild essential hypertension (World Health Organization stages I to II). Two-dimensional-guided M-mode echocardiography and 24-hour ambulatory blood pressure (BP) monitoring was performed in each subject. Simultaneously, we measured 24-hour urinary sodium excretion, 24-hour urinary aldosterone, and serum aldosterone concentration at baseline and after increasing oral salt intake to suppress aldosterone secretion. In all subjects LV mass correlated with body mass index (r = 0.42, p <0.001) and both 24-hour ambulatory systolic (r = 0.28, p <0.05) and diastolic (r = 0.25, p <0.05) BP. Changes in urinary sodium excretion correlated inversely with changes in serum aldosterone concentration (r = -0.28; p <0.05). Urinary aldosterone concentration after salt loading decreased in normotensive (10.98 vs 7.44 microg/24 hours; p <0.02) but not in hypertensive (9.34 vs 10.51 microg/24 hours; p = NS) subjects. Serum and urinary aldosterone levels at baseline were not related to LV structure or function. In contrast, after increasing oral salt intake, urinary aldosterone concentration was related to LV mass (r = 0.43; p <0.01) and impaired midwall fractional fiber shortening (r = -0.33; p <0.02) in all subjects, independent of 24-hour ambulatory BP. Subgroup analysis revealed that this was significant only in hypertensive (r = 0.46; p <0.01 and r = -0.44; p <0.02, respectively) but not in normotensive (r = 0.28 and -0.16; p = NS for both, respectively) subjects. Consistently, the greater serum aldosterone remained after increasing oral salt intake, the greater was LV mass (r = 0.35; p <0.01). The latter was found in hypertensive subjects (r = 0.44; p <0.02), independent of 24-hour ambulatory BP, but not in normotensive subjects (r = 0.025; p = NS). Inadequate suppression of aldosterone in response to an increase in oral salt intake is related to LV structural and functional changes in hypertensive subjects. Thus, our results support experimental data indicating that aldosterone affects LV structure and function in humans and that this effect is BP independent.     

Cardiac structure and function in renovascular hypertension produced by unilateral and bilateral renal artery stenosis

To evaluate cardiovascular status in human renovascular hypertension, quantitative echocardiographic findings were compared in 42 patients with arteriographically documented renovascular hypertension and 46 age- and sex-matched patients with essential hypertension. Left ventricular (LV) fractional shortening, a measure of systolic performance at rest, was subnormal (less than 26%) in 8 of 42 renovascular hypertensive patients (19%), 0 of 42 essential hypertensive patients (p less than 0.005) and 1 of 79 normal subjects (1%) (p less than 0.005). Fractional shortening was equally reduced in patients with arteriosclerotic and nonarteriosclerotic causes of renal artery stenosis (32 +/- 9% vs 32 +/- 6%, both p less than 0.025 compared with 36 +/- 5% in patients with essential hypertension). The depressed function in renovascular hypertension appeared to be a result of greater LV dilation (p less than 0.02) and septal but not LV free wall hypertrophy (p less than 0.01) that failed to offset the pressure load, allowing end-systolic stress, a measure of myocardial afterload, to increase to abnormal levels (101 +/- 47 X 10(3) dynes/cm2, p less than 0.001 vs 68 +/- 19 in essential hypertension). These data indicate that human renovascular hypertension is associated with more adverse cardiac involvement than essential hypertension of similar severity. In addition, the 14 patients with bilateral renovascular stenosis had a higher cardiac index (3.9 +/- 1.1 liters/min/m2) than the 28 with unilateral stenosis (3.2 +/- 1.1 liters/min/m2, p less than 0.05). This result supports the proposition that bilateral renovascular disease is analogous to 1-clip 1-kidney experimental renovascular hypertension, while unilateral renovascular disease resembles the 1-clip 2-kidney model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Capillary recruitment is impaired in essential hypertension and relates to insulin's metabolic and vascular actions

OBJECTIVE: In patients with essential hypertension, defects in both the metabolic and vascular actions of insulin have been described. Impaired microvascular function, a well-established abnormality in essential hypertension, may explain part of these defects. In the present study we investigated whether microvascular function is impaired in essential hypertension and relates to insulin's metabolic and vasodilatatory actions. METHODS: We measured 24-h ambulatory blood pressure, capillary recruitment after arterial occlusion, and skin blood flow responses to iontophoresis of acetylcholine and sodium nitroprusside in 18 subjects with untreated essential hypertension and in 18 control subjects. Whole body insulin sensitivity and leg insulin-mediated vasodilatation were assessed with the hyperinsulinaemic clamp technique and plethysmography. RESULTS: Hypertensive, as compared to normotensive, subjects had a decreased insulin sensitivity (0.8+/-0.3 vs. 1.7+/-0. 6 mgkg(-1)min(-1) per pmoll(-1); P<0.001), capillary recruitment after arterial occlusion (21.5+/-5.8 vs. 45.9+/-10.4%; P<0.001), acetylcholine-mediated vasodilatation (331+/-84 vs. 688+/-192%; P<0. 001), and insulin-mediated vasodilatation (median 29.3 vs. 47.2%; P<0.05). Correlation analyses with adjustment for sex, age, body mass index and waist-to-hip ratio showed significant relationships of capillary recruitment after arterial occlusion with blood pressure (r=-0.68; P<0.01), insulin sensitivity (r=+0.55; P<0.01) and insulin-mediated vasodilatation (r=+0.51; P<0.05), which extended from the normotensive to the hypertensive range. CONCLUSION: Skin microvascular function is associated with blood pressure and insulin's metabolic and vasodilatatory actions, both in normotensive and hypertensive subjects. These findings offer a potential mechanistic explanation of the links among insulin resistance, impaired insulin-mediated vasodilatation and hypertension.     

The Diagnostic Value of the 24 Hour Integrated Concentration of Plasma Aldosterone

The 24-hour urinary excretion rate of aldosterone, the 24-hour integrated concentration of plasma aldosterone (IC-ALDO) and the morning plasma aldosterone levels from a single, discrete venipuncture of 92 subjects (30 normal subjects, 62 patients with mild, essential hypertension) were compared, using the variance ratio method, to 12 patients with primary aldosteronism.

The variance of the IC-ALDO was significantly lower than the respective variances of the 24-hour urinary excretion of aldosterone (P < 0.01) and of the discrete, morning plasma levels of aldosterone (P < 0.01).

The clinical usefulness of this diagnostic procedure depends on its ability to discriminate between healthy subjects and various hypertensive patients. Because of its narrower variance and enhanced discriminatory ability, the 24-hour IC-ALDO may have useful application in diagnosis of various disorders of aldosterone secretion. We have found the IC-ALDO completely separated 11 of 12 primary aldosteronism patients (mean 36±17) from essential hypertensive controls (mean 9.6±4.1)(P < 0.01). When IC-ALDO was combined with integrated concentration of plasma renin activity in an ALDO/RENIN ratio, all 12 primary aldosteronism patients were diagnosed.