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Biomedical subjects

F C Luft

Publications and source records attributed to F C Luft.

At least 19 recordsLinked to original sources
PubMed1992

The influence of age on renal function and renin and aldosterone responses to sodium-volume expansion and contraction in normotensive and mildly hypertensive humans.

To determine the effects of age on the responses of renin, aldosterone (PA), sodium excretion, and renal function to provocative maneuvers, we performed volume expansion and contraction in 390 normotensive and 212 hypertensive subjects in the second to seventh decades of life. The subjects were classified as Na-sensitive if their mean blood pressure was 10 mm Hg or more higher after volume expansion than volume contraction. Sodium sensitivity was associated with hypertension and increasing age. Plasma renin activity decreased with age under basal, stimulated, and suppressed conditions; the decrease was greater in hypertensives than in normotensive persons. The PA values were greater in hypertensives than in normal subjects after volume expansion. There was an age-related decrease in PA values after volume contraction in normal, but not in hypertensive, persons. With volume expansion, hypertensive persons exhibited "exaggerated natriuresis." There was an age-related increase in natriuresis in both groups; the increase was greater in hypertensives than normal subjects. Creatinine clearance decreased with age; however, the rate of decrease in this cross-sectional study was not different in hypertensive and normotensive subjects. These observations may have a bearing on why NaCl affects the blood pressures of older individuals more than younger persons.

Adolescent↗
PubMed1992

New classes of antihypertensive drugs and new findings with established agents.

Research on antihypertensive drugs not only provides new information on presently used agents but also leads to the introduction of exciting new compounds. Several important clinical trials involving currently available drugs have been published recently. Angiotensin-converting enzyme inhibitors improved survival in patients with milder degrees of congestive heart failure, which indicates that they have become the cornerstone of treatment for this condition. Angiotensin-converting enzyme inhibitors delayed or prevented the development of diabetic proteinuria (> 200 micrograms/min) in a placebo-controlled randomized trial. Further, enalapril was more effective than metoprolol in reducing the rate of decline in renal function in patients with type I diabetes. Calcium channel blockers protected against acute renal failure in patients after renal transplantation in two separate studies. Calcium channel blockers were shown to promote natriuresis, with negative sodium balance the same as that associated with thiazide diuretics. The voltage-dependent calcium channel has been cloned, and the binding sites of the three classes of calcium channel blockers are now known. beta-Blockers and thiazide diuretics were the drug treatments in the Systolic Hypertension in the Elderly Program trial and in the Swedish Trial in Old Patients with Hypertension study (patients 65 to 85 years). In both investigations, stroke and cardiovascular events were significantly reduced by these conventional inexpensive agents. Clonidine was found to lower blood pressure primarily by its interaction with the imidazole receptor rather than the alpha 2 receptor. Elucidation of the imidazole receptor promises to shed light on physiologic mechanisms as well as lead to the introduction of new agents, such as moxonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene.

Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin activity. We tested the hypothesis that these rats exhibit an increase in vascular angiotensin formation caused by the presence of the transgene. We measured the release of angiotensins I and II from isolated perfused hindquarters by high-performance liquid chromatography and radioimmunoassay. Female rats heterozygous for the transgene had significantly elevated mean arterial pressure compared with control rats (189.3 +/- 9.5 versus 110.0 +/- 5.4 mm Hg, p less than 0.05). Plasma angiotensin II was significantly decreased in transgenic rats. Transgenic rat hindquarters released more angiotensin I (121 +/- 37 versus 39 +/- 12 fmol/30 min, n = 7 each) and more angiotensin II (210 +/- 21 versus 62 +/- 12 fmol/30 min, p less than 0.05, n = 7 each) than control rat hindquarters. Captopril increased angiotensin I release and decreased angiotensin II values in both transgenic and control rat hindquarters. Bilateral nephrectomy 24 hours before hindquarter perfusion greatly reduced angiotensin release from control rat hindquarters but not from transgenic rat hind limbs. We also tested for the presence of Ren-2 messenger RNA in mesenteric and aortic tissue by RNase protection assay and Northern blot analysis. We found that Ren-2 messenger RNA was present in mesenteric and aortic tissue of transgenic but not of control rats. We conclude that the Ren-2 transgene is expressed in vascular tissue of transgenic rats and may be responsible for substantial increases in vascular angiotensin formation.

Angiotensin II↗
PubMed1992

Amelioration of ischemic acute renal failure by dietary fish oil administration in conscious dogs.

The hypothesis that dietary fish oil would protect dogs from ischemic acute renal failure was tested. Fish oil (eicosapentaenoic acid, 55 mg/kg per day, and docosahexaenoic acid, 40 mg/kg per day was given to eight instrumented, female, beagle dogs for 6 wk, while seven control dogs received vehicle. After 3 wk, unilateral nephrectomy was performed and a pneumatic cuff with flow probe was placed around the remaining renal artery of each dog. Three weeks thereafter, the cuff was inflated for 120 min. Renal function, RBF, and prostanoid excretion were measured 24 and 72 h after ischemia. In dogs receiving fish oil, blood pressure, GFR, RBF, renal vascular resistance (RVR), cholesterol, triglycerides, and prostanoid excretion were measured weekly for 6 wk. Further, cytosolic calcium was measured before and five times after fish oil. Blood pressure decreased, serum cholesterol and triglycerides decreased, and the cytosolic calcium within platelets decreased. The urinary excretion (expressed as picograms per milligram of creatinine) of the thromboxane (TX) metabolite TXB2 and the excretion of prostaglandin (PG)E2, as well as the excretion of the PGI2 metabolite 6-keto PGF1 alpha were decreased. GFR, RBF (Cl inulin and Cl para-aminohippuric acid), and RVR were not influenced by fish oil. Unilateral nephrectomy decreased GFR and RBF and increased RVR as expected, whereas it further decreased prostanoid excretion. Acute renal ischemia caused a significant, reversible decrease in GFR and urine volume in vehicle-treated animals, whereas no significant effect on renal function or urine volume was observed in animals pretreated with fish oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Definitions and characteristics of salt-sensitivity and resistance of blood pressure: should the diagnosis depend on diastolic blood pressure?

To elucidate the importance of diastolic blood pressure in the definition of salt-sensitive hypertension, we studied 54 male subjects, 36 of whom had untreated, mild essential hypertension. The subjects received a 120 mmol/d Na (as the chloride salt) diet for six days. Thereafter they received a 10 mmol/d Na diet for eight days followed by a 400 mmol/d Na diet for another 8 days. Blood pressure was measured hourly "around the clock" on the last day of each diet; the averaged systolic, diastolic and mean blood pressure values were compared. In 22 subjects diastolic blood pressure increased, when salt intake was increased from 10 to 400 mmol/d. In 18 of these 22 subjects systolic blood pressure increased as well. In 20 subjects, systolic blood pressure increased with salt loading while diastolic blood pressure decreased. In 13 subjects both systolic and diastolic blood pressure decreased with increased salt intake. We defined those subjects showing an increase in diastolic blood pressure as salt-sensitive. If mean blood pressure were used to define salt-sensitivity, 8 of our subjects would have been labeled as salt-sensitive who actually decreased their diastolic blood pressure with salt loading. We suggest that consideration of systolic and diastolic blood pressure responses gives better insight into identifying volume and resistance-related phenomena in salt-sensitive hypertension, than does the consideration of mean blood pressure alone. The definition of salt-sensitivity may require reassessment.

Adult↗
PubMed1992

Effect of antihypertensive therapy on the progression of non-diabetic renal disease.

There is a clear, inverse association between the level of blood pressure and the progression of renal disease. This association appears to extend well within the "normotensive" blood pressure range. Currently, there are no absolutely incontrovertible data from prospective, randomized trials in humans documenting that high blood pressure is the cause of an accelerated loss of GFR, or that the loss in renal function can be prevented by lowering blood pressure below 140/90 mmHg. Nevertheless, an aggressive lowering of blood pressure in patients with hypertension and renal disease seems reasonable and desirable. First, the control of blood pressure lowers the "all causes" risk of cardiovascular morbidity and mortality in all patients with elevated blood pressure. Second, any detrimental effects on GFR are uncommon or transient in these patients. Third, the beneficial effects on GFR are firmly supported in animal studies and in humans with malignant hypertension. Fourth, a growing body of evidence from human trials supports the inverse correlation between blood pressure and decrease in GFR, even below a level of 140/90 mmHg. The evidence for these conclusions is reviewed.

Antihypertensive Agents↗
PubMed1992

Sodium kinetics in salt-sensitive and salt-resistant normotensive and hypertensive subjects.

OBJECTIVE: To test the hypotheses that sodium kinetics are not affected by blood pressure, salt sensitivity, salt resistance or race, and that the kinetics of sodium balance are not a first-order process. DESIGN, PARTICIPANTS AND INTERVENTIONS: Two studies were conducted. In the first, 18 normotensive and 36 hypertensive men and women were given sodium at 120 mmol/day for 6 days, followed by 10 mmol/day for 8 days, then 400 mmol/day for 8 more days. Salt sensitivity was defined as an increase in diastolic blood pressure from the 10 to the 400 mmol/day intake. Salt resistance was defined as no increase, or a decrease in diastolic blood pressure with the increased sodium intake. In the second study, 12 white and 12 black normotensive men ingested sodium at 10, 200 or 400 mmol/day in random order, each for 7 days. All urine was collected in both protocols. SETTING: Metabolic ward at the University of Greifswald (Greifswald, Germany; study 1), and Clinical Research Center (Indiana University, Indianapolis, Indiana, USA; study 2). MAIN OUTCOME MEASURE: In addition to conventional statistics, a pharmacokinetic analysis was carried out to determine the elimination rate constant and half-life. RESULTS: In the Greifswald study, when the sodium intake was decreased, a longer half-life was determined for the salt-sensitive than the salt-resistant hypertensive subjects. The half-life for the normotensive salt-sensitive and salt-resistant subjects did not differ. When the sodium intake was decreased, a monoexponential equation fitted the data for all subjects; when the sodium intake was increased, only data for half the subjects could be fitted to the same equation. In the Indianapolis study, black race had a significant influence upon urinary sodium excretion. Furthermore, the half-life for sodium elimination was dependent upon sodium intake; namely, the greater the intake, the longer the elimination half-life. CONCLUSIONS: The time required to reach sodium balance may increase following salt-sensitive increases in blood pressure rather than precede them. Race influences the time required to achieve salt balance. Sodium kinetics are not a first-order process.

Adult↗
PubMed1992

Effects of angiotensin-converting enzyme inhibition in diabetic rats with reduced renal function.

To test the effect of converting enzyme inhibition (CEI) on diabetes, with or without renal insufficiency, we studied streptozotocin-induced diabetic rats, with or without reduced renal mass, which were treated with insulin in sufficient amounts to maintain glucose values in the mild to moderately hyperglycemic range. We found that diabetes increased glomerular filtration rate (GFR) (inulin clearance, 2.3 +/- 0.5 ml/min vs 1.9 +/- 0.1 ml/min; p < 0.05) and blood pressure (137 +/- 15 mm Hg vs 116 +/- 6 mm Hg; p < 0.05) but did not increase plasma atrial natriuretic peptide (ANP) values, when compared with control rats (72 +/- 38 vs 68 +/- 24 pg/ml). CEI decreased GFR and blood pressure to control values. In rats with diabetes and concomitantly reduced renal mass, hypertension, elevated ANP values, proteinuria, and glomerulosclerosis were prominent features. CEI was associated with reduced blood pressure (172 +/- 17 mm Hg vs 138 +/- 15 mm Hg; p < 0.05), without a concomitant decrease in GFR (1.1 +/- 0.1 ml/min vs 1.1 +/- 0.1 ml/min). Further, CEI reduced the elevated ANP values (140 +/- 34 pg/ml vs 66 +/- 19 pg/ml; p < 0.05) to those of control rats. CEI reduced proteinuria by 50% and ameliorated the histopathologic changes. In separate experiments, rats with 5/6th nephrectomy and hypertension but without diabetes were also found to have elevated ANP levels that decreased to control values with CEI. The data speak for a renal protective effect of angiotensin I-converting enzyme inhibition in this model but do not support a specific role for ANP in the model of diabetes with concomitantly reduced renal mass.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Are calcium antagonists of value in ameliorating the course of chronic renal disease?

Renal protection is defined as an attenuation or significant slowing of the irrevocable decrease in renal function over time, which occurs subsequent to renal dysfunction. Control of systemic hypertension by whatever means exerts a renal protective effect. Evidence suggesting a specific action of individual antihypertensive agents is less certain. Calcium antagonists may exert a specific renal protective effect. Experiments in rats with reduced renal mass, desoxycorticosterone-induced hypertension, chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view. In three crossover trials, calcium antagonists reduced proteinuria in patients with type 2 diabetes mellitus. Preliminary data from a single prospective trial in patients with renal insufficiency offer additional support; however, definitive conclusions cannot be reached without further trials. In particular, comparative trials of different classes of antihypertensive agents with equal blood pressure control are needed. Thus far, only reducing systemic blood pressure per se has been shown to be of value in attenuating hypertension-induced renal dysfunction in humans.

Animals↗
PubMed1991

The effect of a household partner and home urine monitoring on adherence to a sodium restricted diet.

To evaluate the effects of social support and home urine monitoring on success with dietary sodium reduction, 114 essential hypertensive adults and a household partner were recruited. One of the pair was required to be the food preparer. Patients with their partners were randomly assigned to either an active or passive partner condition. During dietary counseling in the active condition, both patient and partner were involved in instructions to change their diet to reduce their daily sodium intake to 80 mmol or less. In the passive condition, the partners were present during the dietary counseling, but no effort was made to involve them directly in the instruction or to encourage them to make personal dietary changes. Patients and active partners collected two 24-hr urine collections between each of the first two counseling sessions and received feedback on the sodium results by a telephone call. In the passive partner condition, only patients collected urine for feedback. At the end of the 6 week instructional period, all patients and partners collected a 24-hr urine and had their blood pressure assessed. Half of each group was also randomly assigned to have access to a system for periodic home-monitoring of urine for sodium content during a 3-month period beginning at week 6 of the study (immediate). The delayed feedback group received the home-monitoring three months after completion of the dietary instruction. All patients, but only active partners, used the feedback system during their assignment periods and collected a 24-hr urine monthly between 6 and 30 weeks of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Diet, Sodium-Restricted↗
PubMed1991

Long-term effect of nifedipine and hydrochlorothiazide on blood pressure and sodium homeostasis at varying levels of salt intake in mildly hypertensive patients.

To elucidate and compare the effects of nifedipine (NIF) and hydrochlorothiazide (HCTZ) on blood pressure (BP) and sodium (Na) balance, we conducted a randomized, double-blind, crossover study with 50 mg/day HCTZ and 90 mg/day NIF (as the sustained-release gastrointestinal therapeutic system preparation) in 10 mildly hypertensive patients over approximately 8 weeks. Prior to treatment, the subjects were brought into balance at an intake of 150 mmol/day. During treatment, Na intake was lowered and raised to 50 and 300 mmol/day, respectively, in random order. Then, the subjects were brought into balance on treatment at a level of 150 mmol/day. Balance observations were made during and after the drugs were discontinued. Both HCTZ and NIF lowered BP similarly. When Na intake was lowered from 150 to 50 mmol/day, a significant decrease in diastolic BP was observed with HCTZ. Increasing Na intake to 300 mmol/day did not affect BP. At an intake of 150 mmol/day, HCTZ caused prompt natriuresis, with a negative balance of 150 mmol by 3 days. No initial natriuresis could be shown with NIF. Decreasing Na intake to 50 mmol/day caused prompt negative Na balance with both drugs; increasing it to 300 mmol/day was associated with +150 mmol Na balance with HCTZ while no significant increase was seen with NIF. Discontinuing both drugs caused prompt increase in BP and Na retention over 6 days, which was not different for the drugs. Plasma renin activity (PRA) increased with HCTZ but not with NIF. Further, changing Na intake affected PRA with HCTZ. With NIF, PRA appeared to be uncoupled from the effects of dietary Na intake. In contrast to HCTZ, no adverse metabolic effects were observed with NIF. The data suggest that NIF results in chronic mild natriuresis similar in magnitude to HCTZ. The PRA appears inactivated, although not lowered. The effects of NIF on BP may be at least in part related to the natriuresis and blunting of PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Heterogeneity of hypertension: the diverse role of electrolyte intake.

Nonpharmacologic approaches to treating patients with hypertension are both medically worthwhile and laudable as a public health goal. Reduced salt intake has been the primary dietary measure, but now attention is being directed at potassium, calcium, magnesium, and the anions accompanying these cations. The importance of total caloric intake and of confounding dietary variables such as alcohol consumption are also being acknowledged. It is important to recognize that nutrients are not ingested in isolation, but as interactive constituents of a total diet. This principle may account for some of the heterogeneity of the human blood pressure response to variations of individual electrolyte intake. Moreover, failure to appreciate the heterogeneity and interactive influences may result in other than the desired effect in the population at risk.

Animals↗
PubMed1991

Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological responses.

To identify characteristics that may contribute to salt sensitivity, we conducted studies of normal subjects who are at risk for hypertension, namely blacks, subjects older than 40 years of age, and first-degree relatives of subjects with essential hypertension. We also formulated definitions for salt sensitivity and resistance with a short-term volume expansion and contraction protocol and additionally from data derived from studies of long-term reduced dietary salt intake. We examined the effects of augmented potassium and calcium intake and also those of sodium as the chloride or the bicarbonate salt. Finally, we sought genetic markers that are associated with salt sensitivity. We found that salt sensitivity is a function of age and is more common in blacks than whites. These groups also have relatively delayed acute salt excretion compared with controls. We were unable to identify effects of gender. Haptoglobin phenotypes (HP 1-1) may facilitate identification of salt-sensitive individuals. A high potassium intake may make individuals less salt sensitive. Sodium chloride and sodium bicarbonate differ in their effects on blood pressure. Sodium chloride augments urinary calcium excretion, but sodium bicarbonate does not. Differences between susceptible and nonsusceptible groups, together with improved knowledge of electrolyte interactions, may facilitate our understanding of salt-sensitive hypertension.

Aging↗
PubMed1991

[The role of chlorides in sodium-induced "salt-sensitive" hypertension].

Older and more recent evidence indicates that the anion accompanying sodium plays an important role in determining whether or not the administration of a sodium load leads to an increase arterial in blood pressure. This review describes animal and human studies in which blood pressure responses to sodium administration, with or without chloride, were determined. The evidence suggests that sodium and chloride together combine to increase blood pressure in salt-sensitive models and patients. The observations have relevance to the understanding of the pathogenesis of hypertension. They also have clinical relevance, since some food sources may have an abundance of one or the other ion.

Animals↗