摘要:

We compared corticosteroid metabolite excretion rates and patterns in a group of 68 subjects with untreated essential hypertension and a matched group of 48 normotensive control subjects. The ratio of tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone and the ratio of allotetrahydrocortisol to tetrahydrocortisol were significantly higher in the hypertensive group. This is qualitatively similar to the situation found in patients with the syndrome of apparent mineralocorticoid excess or subjects treated with licorice or carbenoxolone where hypertension is known to arise from deficiencies of 11 beta-hydroxysteroid dehydrogenase and 5 beta-reductase activities. The equivalent ratios for corticosterone metabolites were not different between groups, but total corticosterone metabolite excretion was higher in the hypertensive group. Plasma cortisol levels were lower in hypertensive than in control subjects, but corticosterone levels were higher. This evidence supports a previous suggestion that the activities of these two enzymes may be reduced in essential hypertension, but the contribution of these changes to hypertension is not known.

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The present study examined the relation between blood pressure reactivity to cold stimulus and the subsequent development of hypertension based on a follow-up study from 1960 through 1988 of 824 normotensive participants (mean age, 35.8 plus/minus 10.8 years) in the Adult Health Study in Nagasaki, Japan. Hypertension developed in 343 individuals during the 28 years of follow-up, with a mean incidence rate of 24.6 per 103person-years. Confounding variables, including attained age, resting systolic and diastolic blood pressures, and body mass index at baseline, were adjusted using a Poisson regression model. Systolic response was found to be an independent and significant predictor. The relative risk of hypertension for systolic hyperreactors was 1.37, with a 95% confidence interval of 1.10 to 1.71. Diastolic response was significant only when resting diastolic blood pressure was also considered. The cold pressor test appears to be useful if performed on middle-aged subjects older than 40 years at the time of examination, when hypertension is more prevalent. The current results support the hypothesis that hyperreactivity is a predictor of the development of hypertension. (Hypertension. 1995;25:71-76.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We compared the effects of 4 weeks of calcium channel blockade (amlodipine) or converting enzyme inhibition (lisinopril) on blood pressure and renal hemodynamics in a double-blind crossover trial in a group of 20 hypertensive cyclosporine-treated renal transplant patients. Amlodipine (10 mg) was more effective than the same dose of lisinopril in controlling hypertension (mean 24-hour arterial pressure, 111 plus/minus 9 and 115 plus/minus 9 mm Hg, respectively; P < .05). Blood pressure during both treatments was lower than during placebo (124 plus/minus 12 mm Hg, P < .05). Compared with placebo, amlodipine treatment was associated with a significant increase in glomerular filtration rate (10 plus/minus 20%, P < .05) and effective renal plasma flow (27 plus/minus 20%, P < .01) and a decrease in renal vascular resistance (23 plus/minus 18%, P < .01). Renal hemodynamics did not change during lisinopril. Neither drug had an effect on proteinuria. The data indicate that amlodipine is more effective than lisinopril in controlling hypertension in cyclosporine-treated patients and that treatment with amlodipine but not with lisinopril is accompanied by an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. The data suggest that the renin-angiotensin system does not play a main role in determining cyclosporine-associated changes in renal hemodynamics and has a limited role in determining cyclosporine-associated hypertension. (Hypertension. 1995;25:77-81.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The purpose of the present study was to compare the effect of chronic captopril treatment on blood pressure in young and adult spontaneously hypertensive rats (SHR) and to assess the time course for development of hypertension after captopril withdrawal. SHR received drinking water or captopril solution from 4 weeks of age and were instrumented with radiotelemetry devices at 18 weeks of age to allow continuous monitoring of blood pressure. At 23 weeks of age, mean blood pressure in the captopril group was 100 plus/minus 1 mm Hg compared with 157 plus/minus 3 mm Hg in the water group. Pulse pressure also was significantly reduced in the captopril-treated rats. Infusion of angiotensin II into a subset of captopril-treated rats increased pulse pressure and restored blood pressure to levels of water-treated rats. Captopril treatment for 6 weeks in adult, 24-week-old SHR did not reduce blood pressure to the level of rats treated from 4 weeks of age. Ten weeks after cessation of captopril, blood pressure was 125 plus/minus 4 and 144 plus/minus 4 mm Hg in SHR treated with captopril from 4 to 30 and from 24 to 30 weeks of age, respectively, compared with control hypertensive rats with mean blood pressure of 160 plus/minus 6 mm Hg. Results from this radiotelemetry study confirm previous findings that captopril treatment prevents the development of hypertension and produces a persistent reduction of blood pressure after treatment in young SHR. Captopril treatment produced a persistent reduction of blood pressure after discontinuation in adult rats; however, the effect was less than that observed with captopril initiated in young rats. (Hypertension. 1995;25:82-87.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This study examined the effects of ethnicity and hypertension on beta2-adrenergic receptors and on plasma catecholamines in a group of 77 unmedicated mildly hypertensive and normotensive men. Black hypertensive subjects had the most sensitive and white hypertensive subjects the least sensitive beta-receptors (as assessed by isoproterenol-stimulated cyclic AMP in lymphocytes [P = .02]). In contrast, postreceptor adenylate cyclase activation (as assessed by forskolin stimulation) was similar among groups. As with beta-receptor sensitivity, black hypertensive subjects had the highest beta-receptor density and white hypertensive subjects the lowest (P = .03). Blacks demonstrated lower plasma epinephrine values compared with whites (P = .03). Across all subjects, plasma epinephrine was negatively correlated with beta-receptor density (r = -.26, P < .05) and sensitivity (r = -.25, P < .05). There were no group differences in binding affinity to the beta-antagonist iodopindolol. The findings support the notion of increased beta-adrenergic receptors in hypertension in blacks. (Hypertension. 1995;25:88-91.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The objective of this trial was to assess the effects of 6-month daily treatment with two doses of ramipril on left ventricular mass and the dependence of this on blood pressure changes in hypertensive patients with left ventricular hypertrophy. After a selection phase of 4 to 6 weeks with patients under antihypertensive therapy with 20 mg furosemide daily, 115 patients with either controlled or uncontrolled hypertension and left ventricular hypertrophy were randomized in a double-blind manner to receive either placebo (n = 40), 1.25 mg (low dose, n = 38), or 5 mg (regular dose, n = 37) ramipril daily for 6 months. Treatment with furosemide was continued unchanged during this phase. The main outcome measured was left ventricular hypertrophy regression as assessed from central blind reading of echocardiograms recorded at randomization and after 6 months. No significant differences were observed for changes in casual or ambulatory blood pressure between the three groups. Left ventricular mass index was found to be significantly reduced in patients receiving 5 mg ramipril compared with those receiving placebo (-10.8 plus/minus 3.7 versus +4.1 plus/minus 4.0 g/m2, P = .008); in patients receiving 1.25 mg ramipril, the difference was close to borderline significance compared with placebo (-7.0 plus/minus 4.3 g/m2, P = .06). Similar results were observed for changes in left ventricular mass (-20.3 plus/minus 6.6 and -13.0 plus/minus 7.8 g in the 5- and 1.25-mg ramipril groups, respectively, versus +9.1 plus/minus 7.2 g in the placebo group; P = .004 and .04, respectively). In a multiple regression model testing 10 potential explicative variables, we found that this reduction was correlated with treatment, both 1.25 and 5.0 mg ramipril (P = .03 and .01, respectively), and with the baseline value of the left ventricular mass index (P = .005). Changes in ambulatory or casual systolic and diastolic blood pressures were not predictive of changes in left ventricular mass (P = .15 and .16, respectively). Ramipril at 1.25 and 5 mg daily for 6 months can induce left ventricular hypertrophy regression, independent of changes in blood pressure, in patients under furosemide (20 mg/d) antihypertensive therapy. The implications of this regression for cardiovascular morbidity and mortality in hypertensive patients should now be assessed. (Hypertension. 1995;25:92-97.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin. We determined the extent of left ventricular remodeling present in Ren-2 rats at 16 weeks of age by measuring blood pressure, ratio of heart weight to body weight, left ventricular wall thickness, passive (diastolic) left ventricular compliance, and left ventricular collagen content using hydroxyproline and collagen area fraction. Changes in perivascular fibronectin and collagen type I and III were examined with immunohistochemistry. Blood pressure values at time of death were 244 plus/minus 15 mm Hg for Ren-2 rats (mean plus/minus SD, n = 5). Ratios of heart weight to body weight (grams per kilogram) for Ren-2 animals were 4.1 plus/minus 0.2 versus 3.1 plus/minus 0.1 for controls (n = 6, P < .001). Wall thickness values for control animals were 2.6 plus/minus 0.1 versus 4.1 plus/minus 0.4 mm for Ren-2 animals (P < .001). Left ventricular Ren-2 hydroxyproline measurements were significantly decreased (3.4 plus/minus 0.2 versus 4.7 plus/minus 0.9 mg/g dry wt for controls). Significant decreases of approximately 30% were also observed in collagen area fraction in Ren-2 rats. Immunohistochemical and picrosirius red staining indicated increased amounts of perivascular fibrosis in all Ren-2 animals (when compared with controls) with enhanced levels of perivascular fibronectin and type I and type III collagen proteins. Left ventricular compliance measurements indicated a decrease in left ventricular volume for all left ventricular pressures (P = .07). In conclusion, Ren-2 animals at 16 weeks of age demonstrated a substantial degree of cardiac hypertrophy that was accompanied by perivascular but not diffuse fibrosis and a stiffened left ventricle. (Hypertension. 1995;25:98-104.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We have previously reported that addition of 8-bromo-cyclic AMP enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells in vitro. Isoproterenol is known to stimulate the synthesis of hepatic intracellular cyclic AMP via beta-adrenergic receptors. To study the possible effect of beta-adrenergic receptors on the expression of the angiotensinogen gene in mouse hepatoma cells, we transiently transfected them with a fusion gene with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase coding sequence as a reporter, pOCAT (ANG N-1498/+18). The addition of isoproterenol (10-9to 10-5mol/L) alone had no stimulatory effect on the expression of pOCAT (ANG N-1498/+18). In the presence of dexamethasone (10-6mol/L), however, isoproterenol enhanced the stimulatory effect of the dexamethasone on the expression of pOCAT (ANG N-1498/+18). The enhancing effect of isoproterenol was inhibited by the presence of propranolol (beta1- and beta2-adrenergic receptor antagonist) and ICI 118,551 (beta2-adrenergic receptor antagonist) but not by the presence of atenolol (beta1-adrenergic receptor antagonist). Furthermore, the addition of Rp-cAMP (an inhibitor of protein kinase A I and II) blocked the enhancing effect of isoproterenol. These studies demonstrated that isoproterenol enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells via beta2-adrenergic receptor and cyclic AMP-dependent protein kinase pathways. Our data may be important in understanding the molecular mechanism(s) of the stimulatory effect of catecholamines/glucocorticoid-induced expression of the angiotensinogen gene in the liver. (Hypertension. 1995;25:105-109.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We measured intracellular Calcium2+and isometric force simultaneously in endothelium-denuded mesenteric resistance arteries of 12- to 15-week-old male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, and Wistar rats. Basal Calcium2+did not differ among vessels of these strains (SHR, 86.6 plus/minus 4.5 nmol/L; WKY, 78.5 plus/minus 4.7 nmol/L; Wistar, 83.1 plus/minus 3.9 nmol/L). Myofilament Calcium2+sensitivity was determined by measuring the intracellular Calcium2+and force responses to cumulative addition of extracellular Calcium2+(0.025 to 2.5 mmol/L) in the presence of 100 mmol/L Potassium+or 10 micro mol/L norepinephrine after depletion of releasable intracellular Calcium2+stores. With 100 mmol/L Potassium+, no between-strain differences in active stress, intracellular Calcium2+, or myofilament Calcium2+sensitivity were observed. With 10 micro mol/L norepinephrine, the active stress response of SHR vessels to 0.025 and 0.05 mmol/L Calcium2+was increased compared with both normotensive strains. The intracellular Calcium2+response was not different in vessels of SHR and WKY rats but was depressed in Wistar vessels. Myofilament Calcium2+sensitivity of SHR was elevated compared with both WKY and Wistar rats (P < .05) (ED25for SHR, 74.4 plus/minus 5.1 nmol/L; WKY, 89.8 plus/minus 5.5 nmol/L; Wistar, 86.9 plus/minus 3.4 nmol/L). No strain differences in intracellular Calcium2+or active stress responses of SHR and WKY vessels were detected during cumulative addition of norepinephrine with constant extracellular Calcium2+(1.5 mmol/L). These results indicate that no hypertension-associated defect in vascular Calcium2+handling exists in mesenteric arteries of the SHR. Moreover, although resistance arteries of SHR exhibit enhanced myofilament Calcium2+sensitivity compared with two normotensive strains after depletion of intracellular Calcium2+and activation with 10 micro mol/L norepinephrine, this difference is not observed under the more physiological manipulation of cumulative addition of norepinephrine in the presence of constant Calcium2+. We conclude that enhanced myofilament Calcium2+sensitivity is unlikely to contribute to the hypertension of SHR. (Hypertension. 1995;25:110-116.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Increasing evidence has accumulated for rapid nongenomic steroid actions in various cell systems and, more recently, for rapid aldosterone effects on the Sodium+-Hydrogen+antiport in human mononuclear leukocytes. The aim of the present study was to demonstrate a rapid, nongenomic aldosterone action in rat vascular smooth muscle cells as a key effector cell in cardiovascular regulation. Basal22Sodium+influx in quiescent vascular smooth muscle cells was 22.1 plus/minus 1.9 nmol/mg protein per minute (mean plus/minus SEM, n = 9). Aldosterone (1 nmol/L) stimulated influx to 28.6 plus/minus 1.5 nmol/mg protein per minute after 4 minutes (n = 9, P < .05), with a half-maximal effect between 0.1 and 0.5 nmol/L; the effects were inhibited by ethylisopropylamiloride, the specific inhibitor of the Sodium+-Hydrogen+exchanger, demonstrating the involvement of this transport system in rapid effects of aldosterone. Hydrocortisone (1 micro mol/L) was ineffective, and fludrocortisone and deoxycorticosterone increased influx with half-maximal effects at approximately 0.5 nmol/L. Canrenone, a classic antagonist of aldosterone action, did not inhibit stimulation by aldosterone at a 1000-fold excess concentration. Aldosterone significantly stimulated intracellular inositol 1,4,5-trisphosphate levels (P < .05) after 30 seconds; the inhibitors of phospholipase C, neomycin and U-73122, inhibited aldosterone-stimulated Sodium+influx and increase of intracellular inositol 1,4,5-trisphosphate. The rapid stimulation of sodium transport in vascular smooth muscle cells and the pharmacological characteristics of this effect are clearly incompatible with the classic, genomic pathway of steroid action and represent further evidence for nongenomic effects of aldosterone. (Hypertension. 1995;25:117-123.)

ISSN:0194-911X    

出版商:OVID    

年代:1995

数据来源: OVID