摘要:

A 7-year prospective study of a cohort of 1,458 normotensive adults from Utah pedigrees, screened from 1980 to 1985, was done to determine whether baseline levels of sodium-lithium countertransport were associated with an increased risk of future hypertension. Subsequent new hypertension (n=39) was ascertained in 1989 from detailed follow-up medical questionnaires (67% response). Previous segregation analyses on a subset of these pedigree members who responded (n=342) using family relationships in addition to countertransport levels have shown statistically inferred major gene segregation of sodium-lithium countertransport levels. In the normotensive adults inferred by segregation analysis to carry the recessive major gene for high sodium-lithium countertransport, new-onset hypertension occurred in 18.8% (3 of 16) compared with 3.7% (12 of 326) in the low sodium-lithium countertransport genotype group (relative risk, 4.6 [1.6, 13.9]; p=0.03). However, an elevated baseline sodium-lithium countertransport level without genotype information from segregation analysis did not increase the risk of future hypertension in the complete cohort of adult pedigree members (relative risk, 1.02 [0.85,1.22]). Adjustment for other risk factors reduced the relative risk to 0.90 (0.72,1.11). We conclude that the presence of a major gene for sodium-lithium countertransport or another closely linked gene, rather than the actual level of sodium-lithium countertransport, may increase the risk of hypertension onset High sodium-lithium countertransport levels do not increase the risk of future hypertension for individuals in whom only polygenic and environmental effects determine sodium-lithium countertransport level. Both longer follow-up to increase the number of events and studies in other populations are needed to verify these results. Further characterization of the biochemical and molecular nature of the underlying recessive gene trait is needed to understand how it may increase the risk of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Jacques Pouyss6gur, and Jean-Marc Lalouel The primary abnormalities that contribute to the pathogenesis of human essential hypertension are unknown. The known genetic contribution to this disorder suggests the possible use of genetic linkage analysis to test whether specific candidate genes contribute to the pathogenesis of either essential hypertension or intermediate phenotypes. Among such phenotypes, elevated erythrocyte Na±-Li± countertransport (SIX) is the best known, supporting major gene inheritance by pedigree analysis. Striking similarities between SLC and Na±-H± exchange suggest that mutations at the Na±-H± antiporter gene locus (APNH) might result in elevated SLC and contribute to the subsequent pathogenesis of hypertension. We have tested these hypotheses by genetic linkage analysis, with APNH as a candidate gene. By determining genotypes at APNH and flanking loci in pedigrees that support major gene segregation of elevated SLC, we have excluded linkage of APNH and the major SLC locus with a LOD score of −5.91, an odds ratio of almost 1,000,000 '• 1 against linkage. In the analysis of 93 hypertensive sibling pairs, we have further demonstrated that APNH explains none of the variance in SLC in hypertensive individuals (r2=6xl0∼',/?>0.99). Finally, we have directly tested for linkage of APNH to genes predisposing toward hypertension by linkage in hypertensive sibling pairs. Mean allele sharing at APNH is not greater than expected from random assortment in hypertensive siblings (0.92 versus 1.0,p>0.80), and the upper 95% confidence limit of this value (1.04) indicates that mutations at APNH rarely if ever contribute to the pathogenesis of hypertension in this population. These concomitant results exclude APNH as a candidate gene and demonstrate the use and power of linkage analysis as a means of testing hypotheses in human hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Most antihypertensive drugs have negative effects on metabolic control in diabetic patients. Calcium antagonists have been widely used in antihypertensive treatment of diabetics, although a possible influence on glucose tolerance, insulin secretion, and insulin action is unknown. Therefore, the effect of the calcium antagonist isradipine on glucose tolerance and insulin secretion (75 g oral glucose tolerance test) and on peripheral and hepatic insulin action (euglycemic clamp) was evaluated in 11 type II diabetic patients. All patients were treated with placebo or isradipine for 8 weeks (double-blind, crossover design). A second group of six diabetic patients received a thiazide diuretic, hydrochlorothiazide, according to the same protocol. Systolic blood pressure was significantly lowered after isradipine and hydrochlorothiazide compared with placebo (127±3 versus 139±6 mm Hg and 129±4 versus 142±4, respectively, p<0.05). Fasting blood glucose (190±21 versus 152±15 mg/dl;/><0.01), glucose levels, basal and glucose-stimulated insulin levels were significantly higher after hydrochlorothiazide compared with placebo but remained unchanged after calcium antagonist treatment. Basal hepatic glucose production and peripheral insulin resistance were significantly elevated after hydrochlorothiazide compared with placebo or calcium antagonist therapy. These data indicate that the calcium antagonist isradipine has no effect on glucose tolerance, insulin secretion, and insulin action in type II diabetic patients and might therefore be a useful drug for antihypertensive treatment in diabetes mellitus. However, diuretic treatment can lead to impairment of metabolic control and reduction of insulin action in type II diabetes mellitus.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This study sought to determine if individuals with high-normal blood pressure (diastolic blood pressure of 85–89 mm Hg) progress to hypertension more frequently than those with normal blood pressure (diastolic blood pressure less than 85 mm Hg), thus advancing to a higher cardiovascular risk category. Individuals from the Framingham Heart Study were placed in normal and high-normal blood pressure categories and followed for 26 years for the development of hypertension. With hypertension defined as a diastolic blood pressure of 95 mm Hg or greater or the initiation of antihypertensive therapy, 23.6% of men and 36.2% of women with normal blood pressure developed hypertension compared with 54.2% of men and 60.6% of women with high-normal blood pressure. The relative risk for the development of hypertension associated with high-normal blood pressure was 2.25 for men (95% confidence interval [CI], 1.8–2.8; /?<0.0001) and 1.89 for women (95% CI, 1.5–2.3; /><0.0001). The age-adjusted relative risks estimated by the proportional hazards model were 336 for men and 337 for women (/><0.001). Among those risk factors examined, baseline systolic and diastolic blood pressure, Metropolitan relative weight, and change in weight over time were significant predictors of future hypertension in men and women whose initial blood pressure was normal. For men with high-normal blood pressure, systolic blood pressure and change in weight were identified as risk factors for future hypertension. These results indicate that the probability of individuals with blood pressure in the high-normal range developing hypertension is twofold to threefold higher than in those with normal blood pressure. Therefore, we recommend that persons with high-normal blood pressure be followed up with frequent blood pressure testing and counseled on modification of risk factors.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To examine if chronic sodium loading on the brain produces sustained increases in blood pressure, water intake, and sodium excretion, hypertonic (0.5 M and 1.5 M) and isotonic (0.15 M) NaCI solutions were infused into the third ventricle of Sprague-Dawley rats at a rate of 5.5 Itl/hr for 7 days. Intracerebroventricular infusion of 1.5 M NaCI significantly increased systolic blood pressure during the entire infusion period (±23±5 mm Hg on day 1 and ±15±2 mm Hg on day 7, n=10, mean±SEM). Blood pressure rose insignificantly in the 0.5 M NaCI group, whereas it remained at the baseline levels in the 0.15 M NaCI group. The increases in water intake (day 2), positive water balance (day 2), and negative sodium balance (day 3) were observed in the 1.5 M NaCI group. On day 7, the 1.5 M NaCI group showed hyponatremia and low plasma osmolality and had higher plasma norepinephrine but not vasopressin compared with the 0.15 M NaCI group. In another series of study, depressor response to intravenous hexamethonium (20 mg/kg) in the 1.5 M NaCI group was greater than that in the 0.15 M NaCI group on both day 1 and 7. The depressor response to </(CH2)3Tyr(Me)-arginine vasopressin (10 fig/kg) in the 1.5 M NaCI group was greater on day 1 but not on day 7. These results indicate that sustained sodium stimulus on the central nervous system causes mild hypertension and alters water and sodium balance. The sympathetic nervous system but not vasopressin may play an important role in the chronic phase of central NaCl-induced hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The purpose of this study was to determine if the state of physical training influences sympathetic neural activation during acute stress in humans. We recorded muscle sympathetic nerve activity (microneurography of the peroneal nerve), arterial blood pressure, and heart rate in 12 highly trained, endurance athletes (25 ±1 years, mean±SEM) and 12 untrained subjects (27±1 years) before (supine rest control) and during: 1) lower body negative pressure at − 5, −10, −15, and ‐20 mm Hg (orthostatic stress); 2) isometric handgrip at 30% of maximum (exercise stress); and 3) hand immersion in ice water, that is, the cold pressor test (thermal stress). Body weight was not different in the two groups, but the athletes had a lower body fat content (8.9±13% versus 16.1 ±2.0%,p<0.05). During supine rest, muscle sympathetic nerve burst frequency (24±3 versus 24±2 bursts/min, athletes versus untrained subjects) and burst incidence (36±3 versus 44±4 bursts/100 heart beats) and arterial blood pressure were not different in the two groups, but heart rate was lower in the athletes (54±2 versus 67 ±3 beats/min,/?<0.05). During graded lower body negative pressure, mean arterial pressure and heart rate did not change from control levels in either group, but muscle sympathetic nerve activity increased in a stimulus-dependent manner in both groups; the changes in total minute activity (% control) in the athletes (113±8, 136±11, 174±12, and 209±20) and the untrained subjects (132±6,163±8,210±19, and 262±30) were not different The magnitudes of increases in total minute muscle sympathetic nerve activity in response to isometric handgrip (161 ±15 versus 204±34% control) and the cold pressor test (300±29 versus 255±39% control) was not different in the two groups nor were the associated changes in arterial pressure and heart rate. The results indicate that the sympathetic neural and cardiovascular adjustments to these common laboratory stimuli are not significantly influenced by the individual's level of aerobic conditioning. In addition, the data confirm the previous finding that the state of physical training does not affect muscle sympathetic nerve activity at rest Thus, this factor does not appear to be a primary contributor to the marked intersubject variability observed in sympathetic nerve discharge at rest and in response to acute physical stress in humans.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Compared with the nonnotensive Wistar-Kyoto rat, the spontaneously hypertensive rat exhibits exaggerated alterations in renal sympathetic nerve activity and excretory function during volume expansion (exaggerated natriuresis) and environmental stress (antinatriuresis). The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat and develops hypertension with increased dietary NaCl intake. The present investigation sought to determine whether the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress. Borderline hypertensive rats fed a 1% NaCl diet remained normotensive and exhibited renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress that were similar to those of their Wistar-Kyoto parent Borderline hypertensive rats fed an 8% NaCl diet developed hypertension and exhibited responses that were similar to those of their spontaneously hypertensive parent Thus, the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress. The results suggest that increased dietary NaCl intake is able to induce or unmask the capabilities for these responses, which are genetically conveyed to the borderline hypertensive rat by the spontaneously hypertensive rat parent in latent forms.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The effect of chronic angiotensin I converting enzyme inhibition on the pressure-natriuresis relation was studied in Wistar-Kyoto and spontaneously hypertensive rats. Enalapril maleate (25 mgkg “day” in drinking water) was started at 4–5 weeks of age. At 7–9 weeks of age, the pressure-natriuresis relation was studied while the rats were under Inactin anesthesia 1 week after the right kidney and adrenal gland were removed. Neural and hormonal influences on the remaining kidney were fixed by surgical renal denervation, adrenalectomy, and infusion of a hormone cocktail (330 jtl-kg∼'-min∼') containing high levels of aldosterone, arginine vasopressin, hydrocortisone, and norepinephrine dissolved in 0.9% NaCl containing 1% albumin. Changes in renal function resulting from alterations in renal artery pressure were compared between enalapril-treated and control rats. Mean arterial pressure (±SEM) under anesthesia was 118±5, 94±4, 175±3, and 124±2 mm Hg for control Wistar-Kyoto (n=10), enalapriltreated Wistar-Kyoto (n=10), control spontaneously hypertensive (n=9), and enalapril-treated spontaneously hypertensive (n=9) rats, respectively. When renal artery pressure was set at values above approximately 125 mm Hg, control spontaneously hypertensive rats excreted less sodium and water than control Wistar-Kyoto rats. Enalapril treatment resulted in a significant and similar shift to the left of the pressure-natriuresis relation in both strains of rats so that a lower renal artery pressure was required to excrete a similar amount of sodium when compared with their respective untreated controls. Over the pressure range where differences in the pressure-natriuresis relation were significant, both renal blood flow and glomerular filtration rate were autoregulated and similar in all four groups. The similar effect of enalapril on the pressure-natriuresis curve in Wistar-Kyoto and spontaneously hypertensive rats suggests that the renal effects of angiotensin n are not the primary reason for the difference in the pressure-natriuresis relation in control Wistar-Kyoto and spontaneously hypertensive rats in this preparation.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

In previous studies we found that vasopressin stimulation of both cyclic AMP (cAMP) formation in cortical collecting tubules (CCT) and sodium reabsorption in isolated perfused kidneys was markedly exaggerated in rats with mineralocorticoid hypertension. In the present study, we tested the response (cAMP accumulation) of cortical and outer medullary collecting tubules (OMCT) to vasopressin in two rat models that are resistant to deoxycorticosterone acetate (DOCA) -induced hypertension, the Wistar-Furth strain and NaCl-deficient rats. The blood pressure of normal outbred Wistar rats rose to hypertensive levels (systolic pressure more than 165 mm Hg) during a 5-week treatment with DOCA (10 mg/week) and 1% saline to drink. Significant hypertrophy of the heart and kidneys was also observed. Vasopressin (10∼s M)- induced cAMP formation was enhanced 3.4-fold in the CCT (OMCT unchanged) of hypertensive rats compared with normotensive controls. Significant hypertrophy (as indexed by tubule diameter) of the CCT but not the OMCT was also observed in DOCA-salt hypertensive rats. Restriction of dietary NaCl (0.13% in chow, tap water to drink) completely prevented DOCAinduced hypertension, organ and CCT hypertrophy, and enhancement of vasopressin-stimulated cAMP formation in the CCT. In Wistar-Furth rats, DOCA-salt treatment did not alter blood pressure or cause significant organ hypertrophy. However, DOCA-salt treatment enhanced vasopressin-stimulated cAMP formation by 4.1-fold in CCT of Wistar-Furth rats, with significant tubular hypertrophy in the CCT but not the OMCT. We conclude that DOCA-induced hypertension and changes in CCT function are dependent on excess dietary NaCl. It is unlikely that the alterations in CCT function are the result of hypertension since they are present in DOCA-salt-treated Wistar-Furth rats that remained normotensive. The mechanism for DOCA resistance in the Wistar-Furth strain is extrinsic to vasopressin stimulation of adenylyl cyclase in the CCT.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The purpose of this study was to examine the ability of baroreceptors of renal hypertensive rabbits to reset rapidly during acute changes in arterial pressure. The carotid sinus (CS) was vascularly isolated and baroreceptor activity was recorded during slow ramp increases in CS pressure in hypertensive (one-kidney, one wrap; 127±3 mm Hg) and normotensive (one-kidney, no wrap; 85 ±3 mm Hg) rabbits anesthetized with chloralose. Control measurements were made after holding pressure for 10–15 minutes at the level of arterial pressure recorded before each experiment Baroreceptor threshold pressure (PtJ was higher in hypertensives (78 ±4 mm Hg) compared with normotensives (55 ±3 mm Hg, p<0.05), and nerve activity was less in hypertensives over a wide range of pressure. CS distensibility (sonomicrometers) was not significantly different in the two groups. After increasing holding pressure from control by 30 and 60 mm Hg for 10–15 minutes, the extent of baroreceptor resetting (A P⁁/A holding pressure x 100%) in normotensives was 39±6% and 33±2%, respectively, but only 14±5% and 9±3% in hypertensives (p<0.05). After decreasing holding pressure by 30 and 60 mm Hg, resetting was similar in normotensives (32±6% and 28±3%) and hypertensives (34±3% and 30±4%). In hypertensive rabbits, acute (10–15 minutes) exposure of baroreceptors to normotension (71 ±4 mm Hg) decreased Pa, to 62 ±4 mm Hg and increased nerve activity to levels not significantly different from those of normotensive animals without altering CS distensibility. The results indicate that in chronic renal hypertension: 1) further upward resetting of baroreceptors during acute increases in pressure is suppressed; 2) in contrast, downward resetting during acute decreases in pressure is preserved; 3) baroreceptor activity is restored rapidly after brief exposure of the CS to normal pressure; and 4) changes in CS distensibility do not explain decreased baroreceptor activity in chronic hypertension nor restoration of activity after acute normalization of pressure. Impairment of acute upward resetting and preservation of downward resetting should be beneficial since they would oppose further increases in pressure and facilitate lowering of pressure.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID