ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Vasodilation is one of the most prominent effects of adenosine and one of the first to be recognized, but its mechanism of action is not completely understood. In particular, there is conflicting information about the potential contribution of endothelial factors. The purpose of this study was to explore the role of nitric oxide in the vasodilatory effect of adenosine. Forearm blood flow responses to intrabrachial adenosine infusion (125 [micro sign]g/min) were assessed with venous occlusion plethysmography during intrabrachial infusion of saline or the nitric oxide synthase inhibitor N (G-monomethyl-L-arginine) (L-NMMA) (12.5 mg/min). Intrabrachial infusions of acetylcholine (50 [micro sign]g/min) and nitroprusside (3 [micro sign]g/min) were used as a positive and negative control, respectively. These doses were chosen to produce comparable levels of vasodilation. In a separate study, a second saline infusion was administered instead of L-NMMA to rule out time-related effects. As expected, pretreatment with L-NMMA reduced acetylcholine-induced vasodilation; 50 [micro sign]g/min acetylcholine increased forearm blood flow by 150 +/- 43% and 51 +/- 12% during saline and L-NMMA infusion, respectively (P<.01, n=6). In contrast, L-NMMA did not affect the increase in forearm blood flow produced by 3 [micro sign]g/min nitroprusside (165 +/- 30% and 248 +/- 41% during saline and L-NMMA, respectively) or adenosine (173 +/- 48% and 270 +/- 75% during saline and L-NMMA, respectively). On the basis of our observations, we conclude that adenosine-induced vasodilation is not mediated by nitric oxide in the human forearm. (Hypertension. 1998;31:1061-1064.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Pregnancy-induced hypertension has been suggested to be mediated by several mechanisms, including reduced nitric oxide (NO) synthesis. In this study, the effects of chronic treatment with the NO synthase inhibitor NG-nitro-L-argininemethyl ester (L-NAME) on blood pressure and the underlying changes in vascular reactivity were investigated in virgin and late-pregnancy Sprague-Dawley rats. The systolic blood pressure was 120 +/- 2, 124 +/- 5, 116 +/- 4, and 171 +/- 5 mm Hg in untreated virgin, virgin treated with L-NAME, untreated pregnant, and pregnant treated with L-NAME rats, respectively. The rats were killed, and the thoracic aorta was cut into strips for measurement of active stress in response to alpha1-adrenergicstimulation with phenylephrine and membrane depolarization by high KCl. In pregnant rats, the maximal active stress to phenylephrine (0.31 +/- 0.03x104 N/m2) and the high-KCl-induced active stress (0.55 +/- 0.09x104N/m2) were smaller than those in virgin rats. By contrast, in the L-NAME-treated pregnant rats, the maximal phenylephrine-induced active stress (0.76 +/- 0.1x104N/m2) was greater than that in virgin rats (0.52 +/- 0.1x104N/m2), whereas the high-KCl-induced active stress (1.08 +/- 0.14x104N/m2) was indistinguishable from that in virgin rats (1.03 +/- 0.14x104N/m2). Treatment with L-NAME did not affect the phenylephrine-releasable Ca2+stores in pregnant rats and had minimal effect on active stress in virgin rats. Thus, reduction of NO synthesis during late pregnancy is associated with a significant increase in blood pressure and vascular responsiveness to alpha-adrenergic stimulation, which can possibly be explained in part by enhanced Ca2+entry from extracellular space. However, other mechanisms such as increased myofilament force sensitivity to Ca2+and/or activation of a completely Ca2+-independentmechanism cannot be excluded. (Hypertension. 1998;31:1065-1069.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Cardiovascular disease is the major cause of excess mortality among urban US blacks, but autopsy data comparing black-white differences in underlying pathological causes of cardiovascular death are lacking. We reviewed all 720 adult cases autopsied in 1991 in the New York City Medical Examiner's Office in which the coded cause of death was cardiovascular disease (International Classification of Diseases, 9th Revision, codes 391, 393 to 398, 401 to 404, 410, 411, 414 to 417, 420 to 438, and 440 to 444). After exclusion of 133 cases because race was missing or coded as other than black or white, gender was not coded, or there was an unusual circumstances of death or extreme obesity, 587 cases were available for analysis. There were 314 black and 273 white subjects. Black women were younger than white women at time of death (mean age, 54.7 versus 61.5 years; P<.001), whereas black and white men did not differ in mean age at death. Hypertensive vascular disease was the autopsy cause of death in 42% of blacks compared with 23% of whites (P<.001). Conversely, atherosclerotic heart disease was the autopsy cause of death in 64% of white subjects but only 38% of blacks. These patterns were consistent in both sexes and after adjustment for age. Hypertensive vascular disease was far more common than atherosclerotic heart disease as the cause of death at autopsy among blacks compared with whites in New York City, whereas atherosclerotic heart disease was more common in whites. These findings suggest that ineffective control of hypertension is a major factor contributing to excess cardiovascular mortality among urban blacks. (Hypertension. 1998;31:1070-1076.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The development of the left ventricle parallels body growth. During infancy, the relation between body size and left ventricular (LV) mass is very close. With advancing age, variability of LV mass in relation to body size markedly increases. To test the hypothesis that the age-related increase in variability of LV mass is due to the progressive impact of hemodynamic stimuli on LV growth, quantitative M-mode echocardiograms were obtained in 766 normal-weight, normotensive individuals over a range of ages from 1 day to 85 years (330 female subjects, 373 subjects younger than 18 years). LV mass was linearly related to height2.7 (r2=.69). Prediction of values of LV mass by body size was more accurate at birth and progressively less precise with increasing age. Stroke work (stroke volume times systolic pressure) was closely related to LV mass (r2=.74). The explained variance of LV mass increased from 69% in the univariate regression with height2.7 to 82% in a multivariate model including height2.7, stroke work, and gender. In children and adolescents (younger than 18 years), height2.7 was the main determinant of LV mass, whereas during adulthood stroke work and gender were more important predictors of LV mass than height2.7. Thus (1) the influence of body growth on development of LV mass decreases after early infancy because of both the variability of hemodynamic load and the increasing effect of gender; (2) after adolescence, during adulthood, in normotensive, normal-weight individuals, the impact of hemodynamic load and male gender on LV mass is greater than the one of body size; and (3) an appreciable proportion of variability of LV mass remains unexplained with the studied models. This might be due to genotypic variations and/or measurement error. (Hypertension. 1998;31:1077-1082.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The mechanisms of sodium-induced myocardial hypertrophy and vascular hypertrophy are poorly understood. We tested the hypothesis that a high sodium concentration can directly induce cellular hypertrophy. Neonatal rat myocardial myoblasts (MMbs) and vascular smooth muscle cells (VSMCs) were cultured in a 50:50 mixture of DMEM and M199 supplemented with 10% fetal bovine serum. When the monolayers reached [approximate]80% confluence, normal sodium medium (146 mmol/L) was replaced with high sodium media (152 mmol/L, 160 mmol/L, and 182 mmol/L) for up to 5 days. Increasing sodium from a baseline concentration of 146 mmol/L to the higher concentrations for 5 days caused dose-related increases in cell mean diameter, cell volume, and cellular protein content in both MMbs and VSMCs. Increasing the sodium concentration by only 4% (from 146 mmol/L to 152 mmol/L) caused the following respective changes in MMbs and VSMCs: 8.5% and 8.7% increase in cell mean diameter, 27.6% and 27.0% increase in cell volume, and 55.7% and 46.7% increase in cellular protein content. The rate of protein synthesis, expressed as [(3) H]leucine incorporation, increased by 87% and 99% in MMbs after exposure to 152 mmol/L and 160 mmol/L sodium, respectively, compared with the 146-mmol/L sodium control group. Exposure of MMbs to medium with a sodium concentration of 10% above normal, ie, 160 mmol/L, caused a significant decrease (range, 26% to 44%) in the rate of protein degradation at multiple time points over a 48-hour period compared with normal sodium control cells. The increase in cellular protein content caused by 160 mmol/L sodium returned to normal within 3 days after MMbs were returned to a normal sodium medium. These findings support the hypothesis that sodium has a direct effect to induce cellular hypertrophy and may therefore be an important determinant in causing myocardial and/or vascular hypertrophy in subjects with increased sodium concentration in the extracellular fluid. (Hypertension. 1998;31:1083-1087.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

or=to5 mm Hg increase in diastolic blood pressure after 3 weeks of low salt [<or=to88 mmol/d Na+190 mmol/d Na+] diet). We compared the antihypertensive effect of an angiotensin-converting enzyme inhibitor (enalapril 5 or 20 mg BID) or a calcium channel antagonist (isradipine 5 or 10 mg BID) during alternating periods of high and low salt intake. The main outcome measure was blood pressure change and absolute blood pressure level achieved with therapy. During the high salt diet (314.7 +/- 107.5 mmol/d urinary Na+) there was greater downward change in blood pressure with both enalapril and isradipine compared with the low salt diet (90.1 +/- 50.8 mmol/d Na+); however, the absolute blood pressure achieved in all races was consistently lower on a low salt diet for both agents. Black, white, and Hispanic isradipine-treated salt-sensitive hypertensives demonstrated a smaller difference between high and low salt diets (black, -3.6/-1.6 mm Hg; white, -6.2/-3.9 mm Hg; Hispanic, -8.1/-5.3 mm Hg) than did enalapril-treated patients (black, -9.0/-5.3 mm Hg; white, -11.8/-7.0 mm Hg; Hispanic, -11.1/-5.6 mm Hg). On the low salt diet, blacks, whites, and Hispanics had similar blood pressure control with enalapril and isradipine. On the high salt diet, blacks had better blood pressure control with isradipine than with enalapril, whereas there was no difference in the blood pressure control in whites and Hispanics treated with either drug. Dietary salt reduction helps reduce blood pressure in salt-sensitive hypertensive blacks, whites, and Hispanics treated with enalapril or isradipine. These data demonstrate that controlling for salt sensitivity diminishes race-related differences in antihypertensive activity. (Hypertension. 1998;31:1088-1096.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Recent evidence suggests the existence of several endogenous Na+, K+-ATPaseinhibitors in mammals. Previously, we have shown that the amphibian Na+, K+-ATPaseinhibitor marinobufagenin (3,5-dihydroxy-14,15-epoxy bufodienolide) acts as a vasoconstrictor in isolated rat and human arteries. Mammalian plasma was shown to contain marinobufagenin-like immunoreactive material, which is responsive to saline volume expansion. The present study describes purification of a bufodienolide, which is similar to marinobufagenin, from the urine of patients after acute myocardial infarction with the use of thin-layer chromatography and reverse-phase high-performance liquid chromatography (HPLC). The purified substance cross-reacted with marinobufagenin antibody, demonstrated maximal UV absorbance at 300 nm characteristic of bufodienolides, and eluted from HPLC columns with the same retention time as marinobufagenin. Mass spectrometry of purified material revealed the presence of a substance indistinguishable from amphibian marinobufagenin and having molecular mass of 400 D. The present studies show that one of the human digitalis-like factors may have a bufodienolide structure and is likely to represent marinobufagenin or its isomer, and they suggest a role for this substance in the pathogenesis of myocardial ischemia. (Hypertension. 1998;31:1097-1103.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

To demonstrate potential therapeutic effects of kallikrein gene delivery, we delivered adenovirus (Ad.CMV-cHK) carrying the human tissue kallikrein gene into two-kidney, one-clip Goldblatt hypertensive rats. A single intravenous injection of the recombinant adenovirus caused a delay of blood pressure increase that began 1 day after injection and continued for 24 days. A maximal blood pressure reduction was observed in rats receiving kallikrein gene delivery compared with control rats receiving Ad.CMV-LacZ (160 +/- 5 versus 186 +/- 7 mm Hg, n=6, P<.01). The expression of human tissue kallikrein mRNA was identified in the kidney, heart, aorta, and liver of rats receiving kallikrein gene delivery. Immunoreactive human kallikrein levels were measured in rat serum and urine in a time-dependent manner. Adenovirus-mediated kallikrein gene delivery caused a significant reduction in the left ventricular mass and cardiomyocyte size, as well as an increase in renal blood flow, urine flow, glomerular filtration rates, electrolyte output, and urine excretion. Enhanced renal responses were accompanied by significant increases in urinary kinin, nitrite/nitrate, and cyclic GMP levels. These findings show that the expression of human tissue kallikrein via gene delivery has protective effects against renovascular hypertension and cardiovascular and renal dysfunction. (Hypertension. 1998;31:1104-1110.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We used a modification of the isolated perfused rat heart, in which coronary effluent and interstitial transudate were separately collected, to investigate the localization and production of angiotensin II (Ang II) in the heart. During combined renin (0.7 to 1.5 pmol Ang I/mL per minute) and angiotensinogen (6 to 12 pmol/mL) perfusion (4 to 8 mL/min) for 60 minutes (n=3), the steady-state levels of Ang II in interstitial transudate in two consecutive 10-minute periods were 4.3 +/- 1.5 and 3.6 +/- 1.5 fmol/mL compared with 1.1 +/- 0.4 and 1.1 +/- 0.6 fmol/mL in coronary effluent (mean +/- half range). During perfusion with Ang II (n=5), steady-state Ang II in interstitial transudate was 32 +/- 19% of arterial Ang II compared with 65 +/- 16% in coronary effluent (mean +/- SD, P<.02). During perfusion with Ang I (n=5), Ang II in interstitial transudate was 5.1 +/- 0.6% of arterial Ang I compared with 2.2 +/- 0.3% in coronary effluent (P<.05). The tissue concentration of Ang II in the combined renin/angiotensinogen perfusions (per gram) was as high as the concentration in interstitial transudate (per milliliter). Addition of losartan (10-6mol/L) to the renin/angiotensinogen perfusion (n=3) had no significant effect on the tissue level of Ang II, whereas losartan in the perfusions with Ang I (n=5) or Ang II (n=5) decreased tissue Ang II to undetectably low levels. The results indicate that the heart is capable of producing Ang II and that this can lead to higher levels in tissue than in blood plasma. Cardiac Ang II does not appear to be restricted to the extracellular fluid. This is in part due to AT1-receptor-mediatedcellular uptake of extracellular Ang II, but our results also raise the possibility of intracellular Ang II production. (Hypertension. 1998;31:1111-1117.)

ISSN:0194-911X    

出版商:OVID    

年代:1998

数据来源: OVID