摘要:

To date, no clinical study shows an improvement in coronary flow reserve due to long-term antihypertensive therapy. In view of the contribution of the renin-angiotensin system to the process of hypertensive remodeling of the heart and coronary circulation, angiotensin-converting enzyme (ACE) inhibitors might act as cardioreparative drugs in arterial hypertension. Accordingly, our objective in this investigation was to examine under clinical conditions to what extent long-term antihypertensive treatment with an angiotensin-converting enzyme inhibitor improved the diminished coronary flow reserve in hypertensive patients with microvascular angina pectoris. For the purpose of comparison, we also treated a normotensive control group of 6 patients with hypertrophic nonobstructive cardiomyopathy. Fifteen hypertensive individuals (10 men, 5 women; age, 58 plus/minus 6 years) were treated with enalapril (10 to 20 mg/d; mean, 16.7 plus/minus 4.9 mg/d) for 11 to 13 months. At the end of the treatment period, systolic pressure decreased from 178 plus/minus 14 to 137 plus/minus 12 mm Hg and diastolic pressure from 102 plus/minus 11 to 86 plus/minus 4 mm Hg under ambulatory conditions. Left ventricular muscle mass index decreased by 8%, from 149 plus/minus 32 to 137 plus/minus 28 g/m2(P < .05). Maximal coronary blood flow after dipyridamole was increased by 43%, from 181 plus/minus 69 to 258 plus/minus 116 mL/min per 100 g (P < .001), and minimal coronary vascular resistance was diminished by 29%, from 0.66 plus/minus 0.23 to 0.47 plus/minus 0.24 mm Hg [centered dot] min [centered dot] 100 g [centered dot] mL-1(P < .001) after enalapril treatment. Consequently, the calculated coronary reserve increased from 2.2 plus/minus 0.6 to 3.3 plus/minus 1.2 (P < .001). After enalapril therapy, the functional class of angina pectoris according to the Canadian classification system had changed from 2.5 plus/minus 0.6 to 1.5 plus/minus 0.6 (P < .01). The maximal working capacity had increased from 23.775 plus/minus 3.970 to 26.255 plus/minus 4.598 J (mean plus/minus SE, P < .05). The maximal ST-segment depression at maximal workload was reduced from 0.18 plus/minus 0.02 to 0.06 plus/minus 0.02 mV (mean plus/minus SE, P < .01). In summary, long-term therapy with the angiotensin-converting enzyme inhibitor enalapril must be considered a cardioreparative treatment with respect to the coronary microcirculation in hypertensive heart disease. (Hypertension. 1996;27:1031-1038.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We investigated the effects on the heart of hypertension due to the excess of aldosterone and suppression of the renin-angiotensin system caused by primary aldosteronism with M-mode echocardiography and transmitral Doppler flow velocity measurements. We studied 34 consecutive patients with primary aldosteronism and 34 with essential hypertension individually matched for age, gender, race, body mass index, blood pressure values, and duration of hypertension. The groups were similar in age, body mass index, blood pressure, and duration of hypertension. However, lower serum potassium levels (3.5 plus/minus 0.6 versus 4.1 plus/minus 0.2 mmol/L, P < .0001) and plasma renin activity (0.53 plus/minus 0.45 versus 1.82 plus/minus 1.59 ng Ang I [centered dot] mL-1[centered dot] h-1, P < .0001) and higher plasma aldosterone levels (1107 plus/minus 774 versus 206 plus/minus 99 pmol/L, P < .0001), left ventricular wall thickness, and left ventricular mass index (112 plus/minus 4.7 versus 98 plus/minus 3.7 g/m2, P = .029) were found in patients with primary aldosteronism compared with those with essential hypertension. Similarly, the PQ interval was longer (173 plus/minus 20 versus 141 plus/minus 14 milliseconds, P < .001) in primary aldosteronism than in essential hypertension patients. Significantly more primary aldosteronism than essential hypertension patients had left ventricular hypertrophy or left ventricular concentric remodeling (50% versus 15%, chi2= 11.97, P = .007). Both the E wave flow velocity integral (1063 plus/minus 65 versus 1323 plus/minus 78, P = .013) and the E/A integral ratio (0.91 plus/minus 0.05 versus 1.25 plus/minus 0.08, P < .001) were lower, and atrial contribution to left ventricular filling was higher (53.3 plus/minus 1.5% versus 45.5 plus/minus 1.3%, P < .001) in patients with primary aldosteronism compared with essential hypertension patients. After 1 year of follow-up, highly significant decreases of left ventricular wall thickness and mass were observed in patients treated with surgical excision of an aldosterone-producing tumor, but not in those treated with medical therapy. Thus, in patients with primary aldosteronism, the excess aldosterone with suppression of the renin-angiotensin system is associated with both increased left ventricular mass and significant changes of left ventricular diastolic filling. The former changes appear to be reversible on removal of the cause of excessive aldosterone production. (Hypertension. 1996;27:1039-1045.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The aims of this study were to determine the prevalence of structural changes in the carotid arteries and heart and the correlation between these changes and the commonly recognized cardiovascular risk factors in the general population. Structural changes in the carotid arteries were defined as the intima-media thickness of the artery measured by B-mode ultrasound. Changes in the heart were defined as left ventricular mass index (LVMI) measured by echocardiography. LVMI values greater than 134 g/m2in men and greater than 110 g/m22 mm) was observed in 35% of normotensive subjects and 44% of hypertensive subjects. The prevalence of left ventricular hypertrophy was 13% in normotensive subjects and 19% in hypertensive subjects. Intima-media thickness in the common and bifurcation segments of carotid arteries correlated well with LVMI (r = .20 and r = .19, respectively; P < .01). Intima-media thickness and LVMI were both positively related to 24-hour monitored BP (P < .01). However, in the multivariate analysis, body mass index (P = .027), sex (P < .001), and 24-hour mean BP (P = .025) were the most significant determinants of LVMI, whereas carotid artery intima-media thickness was found to be associated best with age (P < .001), cigarette smoking (P = .009), serum cholesterol (P = .025), serum glucose (P = .038), and nighttime systolic BP (P = .006). Logistic regression analysis confirmed the association between the presence of plaque and age (P < .001), nighttime systolic BP (P < .05), and cigarette smoking (P < .05); a negative association between plaque and the decrease in mean systolic BP from daytime to nighttime was also observed (P < .001). In conclusion, in a general population of unselected middle-aged subjects, carotid wall thickness and LVMI were associated with each other and related to 24-hour BP levels although the major determinants of carotid wall and cardiac structure were different. (Hypertension. 1996;27:1046-1052.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The fibrinolytic system is thought to be impaired in older hypertensive adults, thus contributing to the elevated risk of atherothrombosis, stroke, and acute myocardial infarction in this population. However, studies that have examined the fibrinolytic system in hypertensive individuals have failed to control for the confounding effects of other metabolic risk factors, making it difficult for one to determine the independent effect of hypertension on the fibrinolytic system. The purpose of the present study was to test the hypothesis that the fibrinolytic system is not impaired in older sedentary hypertensive men when the confounding effects of cardiovascular disease, diabetes, and dyslipidemia are controlled. Plasma concentrations of tissue-type plasminogen activator antigen and activity as well as plasminogen activator inhibitor-1 antigen and activity were measured under resting conditions in 12 hypertensive (69.4 plus/minus 1.4 years) and 11 normotensive (65.2 plus/minus 1.3 years) older men. The hypertensive and normotensive subjects had similar anthropometric and metabolic characteristics. There were no significant differences between the hypertensive and normotensive men in tissue-type plasminogen antigen (7.3 plus/minus 0.5 versus 6.1 plus/minus 0.6 ng/mL) and activity (1.8 plus/minus 0.3 versus 1.7 plus/minus 0.2 IU/mL) or plasminogen activator inhibitor-1 antigen (14.1 plus/minus 2.3 versus 10.8 plus/minus 2.2 ng/mL) and activity (17.4 plus/minus 1.2 versus 17.5 plus/minus 1.8 arbitrary units [AU]/mL) levels. In addition, the molar concentration ratio of active tissue-type plasminogen activator to active plasminogen activator inhibitor-1 did not differ between the hypertensive (1:9.7 plus/minus 2.3 mmol/L) and normotensive (1:10.5 plus/minus 2.2 mmol/L) subjects, indicative of no impairment in fibrinolytic potential in either group. These results support the hypothesis that hypertension does not directly result in impaired fibrinolytic function in older adults. Furthermore, our findings suggest that abnormalities in fibrinolytic function in older hypertensive men are likely due to the primary effects of other metabolic disorders that usually accompany hypertension, such as hyperinsulinemia and dyslipidemia. (Hypertension. 1996;27:1053-1058.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Increases in blood pressure during the period of emotional arousal attendant to impending exertion are well documented, yet the etiologic significance of these elevations is unknown. Research suggests that exaggerated cardiovascular responses to psychological stress may be importantly related to hypertension. We examined blood pressure reactivity in anticipation of an exercise stress test in relation to future hypertension in the Kuopio Ischemic Heart Disease Risk Factor Study, a population-based study of middle-aged men from Eastern Finland. Subjects were 508 unmedicated men with resting blood pressure less than 165/95 mm Hg who completed a bicycle ergometer stress test at baseline and whose hypertensive status was assessed at 4 years of follow-up. Systolic and diastolic reactivity were calculated as the difference between blood pressure measured after seated rest on the bicycle ergometer before initiation of exercise and mean seated resting blood pressure measured 1 week earlier. Logistic regression models adjusted for age and resting blood pressure revealed a graded association between quartiles of reactivity and risk of subsequent hypertension (greater or equal to 165/95 mm Hg), with men showing systolic responses greater than or equal to 30 mm Hg or diastolic responses greater than 15 mm Hg at nearly four times the risk of becoming hypertensive (odds ratios, 3.80 [95% confidence interval, 1.90 to 7.63] and 3.65 [95% confidence interval, 1.86 to 7.17], respectively) relative to the least-reactive groups (systolic response, < 10 mm Hg; diastolic response, < 5 mm Hg). Adjustments for traditional risk factors for hypertension did not alter these associations. Results demonstrate the clinical significance of the pressor response in anticipation of exercise and support the hypothesis that cardiovascular reactivity to psychological challenge plays a role in the etiology of hypertension. (Hypertension. 1996;27:1059-1064.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We examined prospectively the relation of nutritional factors with hypertension and blood pressure levels among 41 541 predominantly white US female nurses, aged 38 to 63 years, who completed a detailed semiquantitative food frequency questionnaire in 1984 and were without diagnosed hypertension, cancer, or cardiovascular disease. During 4 years of follow-up, from 1984 to 1988, 2526 women reported a diagnosis of hypertension. Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension. Dietary calcium, magnesium, potassium, and fiber were not significantly associated with risk of hypertension, after adjusting for age, body mass index, alcohol, and energy intake. Among women who did not report hypertension during the follow-up period, calcium, magnesium, potassium, and fiber were each significantly inversely associated with self-reported systolic and diastolic pressures, after adjusting for age, body mass index, alcohol consumption, and energy intake. When the four nutrients were added simultaneously to the regression model, only fiber and magnesium intakes retained significant inverse associations with systolic and diastolic pressures. In analyses of food groups, intakes of fruit and vegetables were inversely associated with systolic and diastolic pressures, and intakes of cereals and meat were directly associated with systolic pressure. These results support hypotheses that age, body weight, and alcohol consumption are strong determinants of risk of hypertension in middle-aged women. They are compatible with the possibilities that magnesium and fiber as well as a diet richer in fruits and vegetables may reduce blood pressure levels. (Hypertension. 1996;27:1065-1072.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Endogenous digitalis-like factors in humans are presumably cardenolides and bufadienolides. To test whether bufadienolide-like substances may circulate in human blood, we used antibodies from rabbits against the bufadienolide proscillaridin A to measure the concentration of cross-reacting material in human plasma with an indirect enzyme-linked immunosorbent assay. IgG had an apparent affinity of 2 x 10-9mol/L for proscillaridin A. It was specific for bufadienolides and did not cross-react with cardenolides or several steroid hormones. Extraction of human plasma with ethanol and fractionation of this extract over a high-performance liquid chromatographic reverse-phase C18 column with a propanol/isopropanol gradient resulted in the separation of three peaks of increasing hydrophobicity (ED1, ED2, ED3) that inhibited the sodium pump of human red blood cells and cross-reacted with proscillaridin A antibodies. The concentration of the proscillaridin A immunoreactivity ED1in normotensive subjects had a geometric mean of 0.1 nmol/L, with a dispersion factor of 8.77. ED1correlated positively in a group of 60 normotensive subjects, 22 patients with hypertension, and 19 patients with chronic renal failure with mean arterial blood pressure (log ED1[nmol/L] = 0.013 x mm Hg - 2.17, r = .25, P < .05), systolic pressure (log ED1[nmol/L] = 0.010 x mm Hg - 2.23, r = .32, P < .01), and pulse pressure (log ED1[nmol/L] = 0.019 x mm Hg - 1.80, r = .38, P < .0001). There was no correlation with other parameters of the donors. We conclude that several substances cross-reacting with proscillaridin A antibodies and inhibiting the sodium pump of human red blood cells circulate in human blood. The level of one of these substances (ED1) correlates with mean arterial and pulse pressures. (Hypertension. 1996;27:1073-1078.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The objective of this study was to examine the effects of wave propagation properties (global reflection coefficient, GammaG; pulse wave velocity, cph; and characteristic impedance, Zo) on the mechanical performance of the coupled left ventricle-arterial system. Specifically, we sought to quantify effects on aortic pressure (Pao) and flow (Qao) while keeping constant other determinants of Paoand Qao(left ventricular end-diastolic volume, Ved, and contractility, heart rate, and peripheral resistance, Rs). Isolated rabbit hearts were subjected to real-time, computer-controlled physiological loading. The arterial circulation was modeled with a lossless tube terminating in a complex load. The loading system allowed for precise and independent control of all arterial properties as evidenced by accurate reproduction of desired input impedances and computed left ventricular volume changes. While propagation phenomena affected Paoand Qaomorphologies as expected, their effects on absolute Paovalues were often contrary to the current understanding. Diastolic (Pd) and mean (Pm) Paoand stroke volume decreased monotonically with increases in GammaG, c (ph), or Zoover wide ranges. In contrast, these increases had variable effects on peak systolic Pao(Ps): decreasing with GammaG, biphasic with cph, and increasing with Zo. There was an interaction between GammaGand cphsuch that GammaGeffects on Pmand Pdwere augmented at higher cphand vice versa. Despite large changes in system parameters, effects on Pmand Pswere modest (< 10% and < 5%, respectively); effects on P (d) were always two to four times greater. Similar results were obtained when the single-tube model of the arterial system was replaced by an asymmetrical T-tube configuration. Our data do not support the prevailing hypothesis that Ps(and therefore ventricular load) can be selectively and significantly altered by manipulating GammaG, c (ph), and/or Zo. (Hypertension. 1996;27:1079-1089.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We determined the effects of angiotensin II (Ang II) on cytosolic free calcium concentrations ([Ca2+]i) in the absence and presence of the selective angiotensin subtype 1 (AT1) receptor antagonist losartan or the selective AT2antagonist PD 123319 in cultured neonatal rat atrial and ventricular cardiomyocytes. We also assessed Ang II receptor density, affinity, and mRNA expression. [Ca2+]iwas measured in single cells microphotometrically and by fluorescent digital imaging with fura 2 methodology. Receptor parameters were assessed by competitive binding studies with125Iodine-[Sar (1), Ile8] Ang II in the presence of increasing concentrations of [Sar1, Ile8] Ang II, losartan, and PD 123319. AT1receptor (types AT1Aand AT1B) mRNA abundance was measured by reverse transcription-polymerase chain reaction. Ang II produced concentration-dependent increases in [Ca2+]i. Basal [Ca2+]ivalues in atrial and ventricular cells were similar but Ang II (10-9mol/L)-induced [Ca2+]ichanges were significantly greater in atrial compared with ventricular cells. Ang II responses were blocked by losartan (10-7mol/L) but not PD 123319 (10-7mol/L). Binding studies demonstrated a single class of high-affinity Ang II binding sites on cardiomyocyte membranes (Kd= 0.71 plus/minus 0.11 micro mol/L).125Iodine-[Sar1, Ile8] Ang II was displaced by losartan but not by PD 123319. AT1receptor mRNA was detected by reverse transcription-polymerase chain reaction in cells from atria and ventricles. In atrial cardiomyocytes, both AT1Aand AT1Breceptor genes were expressed, whereas in ventricular cardiomyocytes, only the AT1Areceptor gene was expressed. These data demonstrate that neonatal cardiomyocytes possess Ang II receptors of the AT1receptor subtype that are linked to [Ca2+]isignaling pathways. The different Ang II-induced [Ca2+]iresponses between atrial and ventricular cells may be related to differences in the distribution of AT1receptor subtype subvariants. (Hypertension. 1996;27:1090-1096.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Tyrosine kinases have been implicated in vascular smooth muscle cell proliferation and contraction. Underlying mechanisms may involve Calcium2+-dependent pathways. This study assesses relationships between angiotensin II (Ang II)-stimulated phospholipase C-mediated Calcium2+transients and tyrosine kinase-dependent pathways in vascular smooth muscle cells. Intracellular free Calcium2+concentration ([Ca2+]i) was measured in primary cultured unpassaged vascular smooth muscle cells derived from mesenteric resistance vessels of Wistar-Kyoto rats with the use of fura 2 methodology. [Ca2+]ieffects of Ang II (1 nmol/L) were determined in vascular smooth muscle cells in which tyrosine kinase pathways were stimulated by insulin (70 micro U/mL; 0.5 nmol/L), insulin-like growth factor-I (1 ng/mL; 0.13 nmol/L), or platelet-derived growth factor-BB (1 ng/mL; 0.04 nmol/L) and in cells in which tyrosine kinase was inhibited by specific inhibitors (1 micro mol/L tyrphostin A-23 and genistein). Ang II elicited a rapid and transient [Ca2+] (i) response (from 94 plus/minus 8 to 239 plus/minus 5.8 nmol/L). Activation of the receptor tyrosine kinase by insulin, platelet-derived growth factor, and insulin-like growth factor-I significantly reduced (P < .01) Ang II-induced [Ca2+]ito 161 plus/minus 7, 189 plus/minus 3.7, and 183 plus/minus 5 nmol/L, respectively. In the presence of tyrphostin A-23 and genistein, Ang II-stimulated [Ca2+] (i) remained persistently elevated and failed to return to basal levels. Tyrphostin A-1, the inactive tyrphostin analogue, had no significant effect on Ang II-induced [Ca2+]i. This study demonstrates that activation of tyrosine kinase pathways reduces Ang II-elicited [Ca2+]iresponses, whereas tyrosine kinase inhibition prevents [Ca2+]irecovery after agonist stimulation. Interaction between tyrosine kinase- and phospholipase C-dependent signaling pathways modulates vascular smooth muscle cell [Ca (2+)]iresponses to Ang II. (Hypertension. 1996;27:1097-1103.)

ISSN:0194-911X    

出版商:OVID    

年代:1996

数据来源: OVID