摘要:

We assessed the impact of initial socioeconomic status and change in socioeconomic status across 10 years, ie, status trajectories, on the development of essential hypertension among black and white young men and women. Three thousand eight hundred twenty-seven normotensive individuals ages 18 to 30 years at study entry were followed for 10 years, with blood pressure, body mass index, and socioeconomic status characteristics measured at years 0, 2, 5, 7, and 10. Socioeconomic status trajectory measures were a new educational degree earned by year 10; difficulties paying for basics during years 2 to 10; and change in income category from year 5 to 10, defined in relation to year 0 status. Hypertension was defined as systolic blood pressure ≥140, diastolic blood pressure ≥90, or antihypertensive medication use at year 10. Reporting difficulties paying for basics at study entry (odds ratio=1.45, 95% confidence interval, 1.05 to 2.02) and continued difficulties during year 2 to 10 follow-up (odds ratio=1.62, 95% confidence interval, 1.04 to 2.53) were independently associated with incident hypertension, adjusted for race-gender group, body mass index, site, age, and initial systolic blood pressure. Decline in income from year 5 to 10 tended to be associated with hypertension,P=0.07, but a new educational degree after study onset was not. Socioeconomic trajectories are independently associated with incidence of hypertension. A dynamic index of socioeconomic status may be a useful concept in understanding the effects of socioeconomic status on the natural history of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Because oxidative stress and inflammation are believed to play roles in the pathogenesis of cardiovascular diseases, oxidative stress in polymorphonuclear leukocytes (PMNs) and mononuclear cells (MNCs) has been measured. A total of 529 subjects participated this study. Intracellular oxidative stress in PMNs and MNCs was measured by gated flow cytometry using carboxyfluorescin diacetate bis-acetoxymethyl ester. C-reacting protein (CRP), insulin action (homeostasis model assessment), and traditional risk factors such as age, gender, body mass index, triglycerides, LDL cholesterol, HDL cholesterol, hemoglobin A1c, and mean blood pressure were also measured. Multiple regression analysis revealed a significant correlation between mean blood pressure and PMN oxidative stress (r=0.104,P=0.018). It also demonstrated a significant correlation between hemoglobin A1cand PMN oxidative stress (r=0.112,P=0.021). A significant correlation was also found between CRP and MNC oxidative stress (r=0.116,P=0.008) by multiple regression analysis. In patients with both hypertension and diabetes, both PMN and MNC oxidative stress was increased (n=21,P=0.022 andP=0.006). These results suggest that both hypertension and diabetes lead to increased oxidative stress of PMNs and MNCs, and that CRP is related to MNC oxidative stress.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Ghrelin, an endogenous ligand for the growth hormone secretagogues, was originally isolated from rat stomach. It stimulates the release of growth hormone from primary pituitary cell cultures. We investigated the plasma concentration of ghrelin peptide in 16 nonpregnant women, 18 normal pregnant women, 20 patients with pregnancy-induced hypertension, and 10 postpartum women. The plasma concentration of ghrelin in nonpregnant women was 239.5±16.9 fmol/mL. The plasma concentration of ghrelin in normal pregnant women at the third trimester was 127.1±5.6 fmol/mL. There was negative correlation between plasma ghrelin concentration and systemic blood pressure in normal pregnant women (systolic:r=−0.564,P<0.05; diastolic:r=−0.610,P<0.01). Pregnant women with pregnancy-induced hypertension (177.9±14.6 fmol/mL,P<0.05) also had significantly higher levels of ghrelin compared with those of normal pregnant women. In addition, there was a significant correlation between plasma ghrelin levels and systemic blood pressure (systolic:r=−0.482,P<0.05; diastolic:r=−0.466,P<0.05). These results suggest for the first time that ghrelin might have some role in cardiovascular control during normal pregnancy and in pathophysiological conditions in pregnancy, such as pregnancy-induced hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. They inhibit cyclooxygenases (COX), preventing the formation of prostaglandins, including prostacyclin and thromboxane. A serious side effect of COX-1 and COX-2 is renal damage. We report here that both a nonselective NSAID (aspirin, acetylsalicylic acid) and COX-2 selective NSAIDs (celecoxib and NS-398) diminished renal prostacyclin and thromboxane concentration in the renal medulla. NSAIDs failed to change COX-2 and iNOS (the inducible form of NO synthase) expression. A NO donor, B-NOD, preserved renal prostacyclin and thromboxane after administration of aspirin. PGI2and COX-2 protein were mainly expressed in the renal medulla, whereas iNOS expression was greater in the cortex. B-NOD preserved renal prostacyclin levels after administration of NSAIDs.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

This study investigated the role of NO in mediating the renal sympathetic nerve–mediated increases in proximal tubular fluid reabsorption (Jva). In inactin-anesthetized Wistar rats, renal sympathetic nerve stimulation (15 V, 2 ms) at 0.75 and 1.0 Hz did not change blood pressure or glomerular filtration rate but did decrease urine flow and sodium excretion in a frequency-related fashion by 40% to 50% at 1.0 Hz (both,P<0.01). Renal nerve stimulation in control animals increased Jva by 11% at 0.75 Hz (P<0.05) and 31% at 1.0 Hz (P<0.01). IntraluminalN&ohgr;-nitro-l-arginine methyl ester (L-NAME) resulted in a higher basal Jva (19%,P<0.05), and renal nerve stimulation had no effect on Jva. When L-NAME plus sodium nitroprusside was present intraluminally, however, there were frequency-dependent increases in Jva that were similar in pattern and magnitude to the control rats. Introduction of the relatively selective nNOS blocker 7-nitroindazole intraluminally, at 10−6and 10−4M, raised basal Jva by 18% and 24%, respectively (P<0.01), and renal nerve stimulation did not change Jva. Intraluminal aminoguanidine (10−4M), a relatively selective iNOS blocker, did not affect basal Jva, which remained unchanged during renal nerve stimulation. These data are consistent with NO exerting a tonic inhibitory action on the basal levels of Jva, which, in part, is caused by NO generated by the nNOS isoform. Moreover, the findings have revealed that the presence of NO is necessary to ensure that renal nerves can stimulate fluid reabsorption by the proximal tubules, requiring NO generated from both nNOS and iNOS.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The objective of the study was to assess the factors related to the occurrence of microalbuminuria during the follow-up of a young adult group with essential hypertension that had not been previously treated. Normo-albuminuric essential hypertensives, <50 years old, who had not been previously treated with antihypertensive drugs and who did not have diabetes mellitus were included. After the initial evaluation, patients were treated using only nonpharmacological measures (n=62), &bgr;-blockers (n=38), ACE inhibitors (n=64), calcium channel blockers (n=8), and several classes (n=15). Measurements were taken for office blood pressure, biochemical profile, and 24-hour urinary albumin excretion at the beginning of the study and were measured yearly during an average of 2.7±1.2 years of follow-up. Among the 187 patients included, 22 (11,7%) developed microalbuminuria (progressors, 4.4/100 patients/y). No differences were present between progressors and those who remained normo-albuminuric (nonprogressors) in terms of age, gender, body mass index, disease duration, blood pressure values, biochemical profile, familial history of diabetes or hypertension, smoking habits, or the presence of EKG left ventricular hypertrophy. The group with the lowest progression rate was the patients treated with ACE inhibitors (n=5; 2.9/100 patients/y), followed by the diet group (n=5; 3.3/100 patients/y) and the &bgr;-blockers group (n=5; 4.1/100 patients/y). When we excluded patients treated with calcium channel blockers or those who changed over time between different classes of treatment, no significant differences in the incidence of microalbuminuria were observed among the groups. Progressors showed higher slopes of fasting glucose (4.78±11.4 versus 0.50±6.8 mg/y,P<0.02) and uric acid (0.58±0.93 versus 0.05±1.10 mg/y,P<0.03) compared with the slopes of nonprogressors. Both the slopes for glucose and systolic blood pressure over time were associated independently with the slope of the logarithm of urinary albumin excretion when adjusted for age, gender, and treatment groups. Cox proportional hazard model for progression of microalbuminuria showed that baseline urinary albumin excretion (risk ratio [RR]=1.06; confidence interval [CI] 95%, 1.01 to 1.11), slope for systolic blood pressure (RR=1.11; CI 95%, 1.03 to 1.20), and slope for glucose (RR=1.08; CI 95%, 1.03 to 1.14) were independently associated to the development of microalbuminuria. In conclusion, in a group of young adults with essential hypertension that had not been previously treated, the main factors influencing the occurrence of microalbuminuria during antihypertensive treatment were the values of microalbuminuria at baseline and the slopes for systolic blood pressure and fasting glucose.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Recent studies have shown that angiotensin-(1-7) (Ang-[1-7]), which is generated endogenously from both Ang I and II, is a bioactive component of the renin-angiotensin system and may play an important role in the regulation of blood pressure. However, little is known about its role in regulating the reactivity of the afferent arteriole or the mechanism(s) involved. We hypothesized that Ang-(1-7), acting on specific receptors, participates in the control of afferent arteriole tone. We first examined the direct effect of Ang-(1-7) on rabbit afferent arterioles microperfused in vitro, and we tested whether endothelium-derived relaxing factor/NO and cyclooxygenase products are involved in its actions. To assess the vasodilator effect of Ang-(1-7), afferent arterioles were preconstricted with norepinephrine, and increasing concentrations of Ang-(1-7) were added to the lumen. We found that 10−10to 10−6mol/L Ang-(1-7) produced dose-dependent vasodilatation, increasing luminal diameter from 8.9±1.0 to 16.3±1.1 &mgr;m (P<0.006). Indomethacin had no effect on Ang-(1-7)–induced dilatation.NG-nitro-l-arginine methyl ester, a NO synthesis inhibitor, abolished the dilatation induced by Ang-(1-7). We attempted to determine which angiotensin receptor subtype is involved in this process. We found that 10−6mol/L [d-Ala7]–Ang-(1-7), a potent and selective Ang-(1-7) antagonist, abolished the dilatation induced by Ang-(1-7). An angiotensin II type 1 receptor antagonist (L158809) and an angiotensin II type 2 receptor antagonist (PD 123319) at 10−6mol/L had no effect on Ang-(1-7)–induced dilatation. Our results show that Ang-(1-7) causes afferent arteriole dilatation. This effect may be due to production of NO, but not the action of cyclooxygenase products. Ang-(1-7) has a receptor-mediated vasodilator effect on the rabbit afferent arteriole. This effect may be mediated by Ang-(1-7) receptors, because angiotensin type 1 and type 2 receptor antagonists could not block Ang-(1-7)–induced dilatation. Thus, our data suggest that Ang-(1-7)opposes the action of Ang II and plays an important role in the regulation of renal hemodynamics.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

B-type natriuretic peptide (BNP) plasma concentrations are raised in patients with heart failure. In several experimental models of cardiac overload, however, BNP mRNA and plasma BNP peptide levels are normal, despite the persistent increase in blood pressure and ventricular hypertrophy. In this study, the role of transcriptional mechanisms in the regulation of BNP gene expression were studied in angiotensin (Ang) II–induced hypertension by injecting DNA constructs containing the BNP promoter (−2200 to 75 bp of the transcriptional start site) linked to luciferase reporter into rat myocardium. Ang II was administered to conscious rats via intravenous infusion for 2 hours or by subcutaneous minipumps for 6 hours, 12 hours, 3 days, 1 week, and 2 weeks. Ang II increased blood pressure and cardiac mass and induced changes in diastolic function. The left ventricular BNP mRNA levels increased 2.2-fold (P<0.001) at 2 hours and peaked at 12 hours (5.2-fold,P<0.001). Thereafter, BNP mRNA levels decreased (1.8-fold induction at 3 days,P<0.05) and returned to control levels at 1 week, despite persistent hypertension and myocardial hypertrophy. Left ventricular BNP peptide concentrations followed the changes in BNP mRNA levels. The BNP promoter was activated 2.7-fold (P<0.05) at 2 hours and remained upregulated up to 2 weeks (2.8-fold,P<0.05) during Ang II infusion, except at 12 hours. These results indicate that posttranscriptional control plays a major role in the regulation of ventricular BNP gene expression in Ang II–induced hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Methylglyoxal can yield advanced glycation end products via nonenzymatic glycation of proteins. Whether methylglyoxal contributes to the pathogenesis of hypertension has not been clear. The aim of the present study was to investigate whether the levels of methylglyoxal and methylglyoxal-induced advanced glycation end products were enhanced and whether methylglyoxal increased oxidative stress, activated nuclear factor–&kgr;B (NF-&kgr;B), and increased intracellular adhesion molecule-1 (ICAM-1) content in vascular smooth muscle cells from spontaneously hypertensive rats. Basal cellular levels of methylglyoxal and advanced glycation end products were more than 2-fold higher (P<0.05) in cells from hypertensive rats than from normotensive Wistar-Kyoto rats. This correlated with levels of oxidative stress and oxidized glutathione that were significantly higher in cells from hypertensive rats, whereas levels of glutathione and activities of glutathione reductase and glutathione peroxidase were significantly lower. Basal levels of nuclearly localized NF-&kgr;B p65 and ICAM-1 protein expression were higher in cells from hypertensive rats than from normotensive rats. Addition of exogenous methylglyoxal to the cultures induced a greater increase in oxidative stress and advanced glycation end products in cells from hypertensive rats compared with normotensive rats and significantly decreased the activities of glutathione reductase and glutathione peroxidase in cells of both rat strains. Methylglyoxal activated NF-&kgr;B p65 and increased ICAM-1 expression in hypertensive cells, which was inhibited byN-acetylcysteine. Our study demonstrates an elevated methylglyoxal level and advanced glycation end products in cells from hypertensive rats, and methylglyoxal increases oxidative stress, activates NF-&kgr;B, and enhances ICAM-1 expression. Our findings suggest that that elevated methylglyoxal and associated oxidative stress possibly contribute to the pathogenesis of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Vascular endothelial growth factor (VEGF) induces hypotension in normotensive subjects, which is considered to be a major side effect for treatment of ischemic diseases. However, the hypotensive effect of VEGF has not been investigated in the setting of hypertension. This study determined effects of VEGF on hemodynamics, pharmacokinetics, and release of NO and prostaglandin I2(PGI2) in vivo and on vasorelaxation of mesentery artery rings in vitro in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Intravenous infusion of VEGF for 2 hours produced a dose-related decrease in arterial pressure, which was enhanced in conscious SHR compared with WKY (P<0.01), and an increase in heart rate in WKY but not in SHR. In response to similar doses of VEGF, compared with WKY, SHR had a higher plasma VEGF level and lower VEGF clearance (P<0.01). Circulating NO and PGI2levels after VEGF administration were not increased in SHR versus WKY, and VEGF-induced vasorelaxation was blunted in SHR versus WKY in vitro, suggesting endothelial dysfunction in SHR. One-week VEGF infusion also caused greater hypotension (P<0.05) in the absence of tachycardia in SHR compared with WKY controls. Thus, despite blunted vasorelaxation in vitro because of endothelial dysfunction, SHR exhibited exaggerated hypotension without tachycardia in response to VEGF, which was independent of NO and PGI2. The exaggerated hypotensive response to VEGF in SHR may be owing to impaired baroreflex function and reduced VEGF clearance. The data may also suggest that more caution should be taken when VEGF is administered in patients with hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID