Search PubMed⌕ Search

Biomedical subjects

F C Luft

Publications and source records attributed to F C Luft.

At least 433 records · Page 24Linked to original sources
PubMed1988

Heritable aspects of salt sensitivity.

Dietary salt reduction is an important nonpharmacologic remedy for mild hypertension as well as a useful adjunct to drug treatment. However, a reduced salt intake diet is not effective in reducing the blood pressure of all hypertensive patients. Several lines of evidence indicate that some patients are salt-sensitive whereas others are salt-resistant. A series of investigations have been conducted showing that the blood pressure responses to either acute salt and volume loading or to a reduced dietary salt intake are normally distributed. Blood pressure, humoral regulators of blood pressure and renal sodium handling are each found to be influenced by genetic variance. The change in blood pressure from dietary salt reduction is influenced by genetic variance as well. Definitions of salt sensitivity and resistance were formulated, and salt sensitivity of blood pressure was found to occur significantly more often in black than in white Americans. Furthermore, preliminary data suggest that measurement of phenotypes of haptoglobin in blood may assist in identifying salt-sensitive and salt-resistant subjects. Trials of a reduced salt intake diet in pharmacologically treated hypertensive patients are currently being conducted. The data suggest that at least half of the patients are salt-sensitive and that their medications may be reduced in response to the intervention. Results of this study may be of relevance to many of the 60 million Americans with hypertension, particularly to those who are black and elderly.

Adult↗
PubMed1988

Dietary sodium restriction as adjunctive treatment of hypertension.

To examine the effect of modest dietary sodium ion restriction in treated hypertensive individuals, we studied 114 hypertensive patients undergoing individualized dietary counseling with a research dietitian to achieve reduction in dietary sodium ion intake. A significant reduction in mean sodium ion intake was achieved after the first of three lessons and was maintained for 30 weeks with no change in potassium ion intake. Significant falls in blood pressure and body weight were observed with no significant correlations noted between the two variables, implying independence of these effects. Individuals compliant with the dietary sodium ion restriction goal (urinary excretion, less than or equal to 80 mmol/d [less than or equal to 80 mEq/24 h]) were more likely to have a reduction in number of medications than those not reaching that goal. Ninety-eight of the 114 patients completed the entire 30 weeks. Patients who dropped out tended to have lower diastolic blood pressures and required fewer medications for blood pressure control than those who completed the 30 weeks. For these reasons, patients in the former group may have been less highly motivated to complete the study. These observations suggest that modest dietary sodium ion restriction is feasible in treated hypertensive patients and that adherence to such a regimen may permit blood pressure control with fewer medications.

Adult↗
PubMed1988

Renal disease and the development of hypertension in salt-sensitive Dahl rats.

To elucidate the role of the kidneys in the development of hypertension in Dahl salt-sensitive (S), as compared to resistant (R) rats of the JR strain, we analyzed functional and morphological changes before and after the administration of an 8% NaCl diet and the onset of hypertension. The diet was begun at six weeks of age and was continued until 12 weeks of age. At six weeks, blood pressure was not different between S and R rats. Hypertension occurred in S rats receiving the 8% NaCl diet at week 8, and in S rats receiving 0.9% NaCl at week 10. Albuminuria and proteinuria were found in S rats prior to the 8% NaCl diet and progressed regardless of diet. Electron microscopy of glomeruli revealed segmental loss of epithelial foot processes in S rats at six weeks prior to the 8% NaCl diet. Mesangial widening, arteriolar myo-intimal cell hyperplasia and interstitial fibrosis occurred in all S rats. Inulin and PAH clearances in S rats decreased with time, the changes being accelerated by the 8% NaCl diet. Micropuncture of S and R rats prior to the 8% NaCl diet revealed no glomerular hypertension in S rats. The number of glomeruli in S and R rats were not different. We conclude that prehypertensive S rats of the JR strain already have albuminuric glomerular disease not associated with reduced number of glomeruli or glomerular hypertension. The renal pathology is accelerated once hypertension develops. A lower NaCl intake delays, but does not prevent renal disease in S rats.

Albuminuria↗
PubMed1988

Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats.

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin-angiotensin-aldosterone system and 18-hydroxydeoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower PCO2 and HCO3- values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

Animals↗
PubMed1988

Effect of a prostacyclin derivative (iloprost) on regional blood flow, sympathetic nerve activity, and baroreceptor reflex in the conscious rat.

We have investigated the hemodynamic actions of iloprost, a stable prostacyclin derivative, in conscious, chronically instrumented rats. Given intravenously by 10-min infusions at doses ranging from 0.0375 to 4 micrograms/min, iloprost lowered mean arterial blood pressure in a dose-dependent and reversible fashion. The effects on blood pressure were accompanied by increases in heart rate (HR); splanchnic nerve activity (SpNA, direct recording); and mesenteric, renal, and hindlimb blood flow (Doppler probes). Doses below the depressor threshold already reduced mesenteric and hindlimb vascular resistance without affecting HR. The reduction of hindlimb resistance outlasted the iloprost infusion period. Chronic sinoaortic deafferentation (SAD) almost abolished the tachycardic reflex responses to intravenous sodium nitroprusside. The reflex increases in SpNA to intravenous iloprost were also largely prevented in SAD animals, but the tachycardic effects of iloprost persisted. In addition, neither beta 1-adrenoceptor blockade alone nor complete cardiac autonomic blockade prevented the heart rate responses to iloprost. Our results show that iloprost is a potent vasodilator that preferentially reduces hindlimb vascular resistance. Low doses of the drug increase regional blood flow without affecting blood pressure or heart rate. The tachycardic effects at higher doses cannot be explained by baroreceptor reflex (BRR) activation alone; they instead suggest a direct action on the heart. The dissociation between vasodilator and depressor effects at low doses may contribute to the therapeutic benefit of the drug in the treatment of vascular disease.

Animals↗
PubMed1988

Facilitation of natriuresis with nifedipine in normal humans.

We tested the effect of dietary potassium (KCl, 20 mEq three times daily), calcium (Ca, 500 mg twice daily), sodium-potassium-dependent ATPase inhibition (digoxin), calcium channel blockade (nifedipine), and placebo on acute natriuresis in 14 normal subjects who received 2 L normal saline intravenously over 4 h. Plasma renin activity (PRA) was increased in subjects receiving nifedipine, while plasma aldosterone (PA) concentrations were not different among the regimens. Only KCl and nifedipine affected sodium excretion compared to controls. KCl and nifedipine increased the amount of sodium excreted after the infusion was terminated. In the case of nifedipine, this natriuresis was sufficient to increase the 24 h sodium excretion on that day to above that of the other regimens.

Adolescent↗
PubMed1988

Hypothalamic GABA suppresses sympathetic outflow to the cardiovascular system.

We studied the cardiovascular effects of altering GABA-ergic tone in the posterior hypothalamus in rats. Animals were equipped with chronic guide cannulas placed in the posterior hypothalamus, arterial and venous catheters, and a bipolar electrode on the splanchnic nerve. Microinjected bilaterally into the posterior hypothalamus in conscious rats, the postsynaptic gamma-aminobutyric acid (GABA) antagonists bicuculline methiodide and picrotoxin rapidly increased heart rate, blood pressure, and sympathetic nerve activity. Microinjection of the GABA agonist muscimol into this same region decreased heart rate, blood pressure, and sympathetic nerve activity in conscious rats. In contrast, muscimol infused into the posterior hypothalamus of anesthetized rats failed to alter heart rate or blood pressure. We conclude that 1) the posterior hypothalamus contains a sympathoexcitatory system that is modulated by changes in GABA-ergic tone and 2) tonic GABA-ergic inhibition is sufficient to completely suppress the activity of this hypothalamic sympathoexcitatory system in anesthetized animals but not in conscious rats.

Animals↗
PubMed1988

Review of salt restriction and the response to antihypertensive drugs. Satellite symposium on calcium antagonists.

We evaluated the response to salt restriction in hypertensive patients receiving drugs. By restricting their salt intake to less than 80 mmol of sodium per day for 3 months, 50% of patients reaching goal compliance were able to discontinue diuretics. The literature also reveals responses to a low salt diet. Salt restriction augmented the hypotensive effect of chlorthalidone in two investigations, but not in another, and the hypotensive effect of beta-blockers in three trials. Sodium intake of 10 mmol/day caused a much greater decrease in blood pressure in response to a single dose of captopril than did a sodium diet of 200 mmol/day. In patients receiving various fixed regimens for 2 months, salt restriction decreased blood pressure in all but those receiving calcium blockers. A single dose of nifedipine lowered blood pressure more in patients receiving 350 mmol of sodium per day than in the same patients given 150 or 10 mmol/day. Verapamil for 3 days was more effective in patients receiving 212 mmol of sodium per day than in the same subjects receiving 9 mmol/day. Nitrendipine caused a greater decrease in diastolic blood pressure in patients who did not reduce salt intake compared to those who did. Salt restriction appears useful in salt-sensitive patients who receive beta-blockers, diuretics, converting enzyme inhibitors, or centrally acting drugs. Calcium channel entry blockers may not require salt restriction to maximize their effect.

Adrenergic beta-Antagonists↗
PubMed1988

Effect of high calcium diet on magnesium, catecholamines, and blood pressure of stroke-prone spontaneously hypertensive rats.

To test the effect of a high dietary calcium intake on blood pressure, we fed stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto rats (WKY) diets containing (a) 0.25% Ca/0.08% Mg, (b) 4.0% Ca/0.02% Mg, and (c) 4.0% Ca/0.08% mg, beginning at 6 weeks of age. SHR-SP and WKY rats receiving 4% Ca with the lower Mg content had lower blood pressures, hypomagnesemia, and hypomagnesuria, and grew poorly. SHR-SP receiving 4% Ca and the higher Mg diet had blood pressures no different from those of rats receiving the 0.25% Ca diet, in spite of having lower body weights. Rubidium flux studies in erythrocytes were not influenced by Ca or Mg in the diets. Plasma phosphate values were moderately reduced in rats receiving 4% Ca diets. Epinephrine and norepinephrine values were higher in SHR-SP than in WKY rats. Norepinephrine increased with stress in both strains, independent of diet. Epinephrine values were lower in SHR-SP receiving the 4% Ca diets and showed less of an increase with stress compared to SHR-SP receiving the 0.25% Ca diet. After 26 weeks of diets, SHR-SP and WKY rats were given 0.9% NaCl in their drinking water. NaCl increased blood pressure in SHR-SP irrespective of Ca content of the diet. These data suggest that a high Ca diet influences Mg homeostasis and adrenal medullary function in SHR-SP. Further, SHR-SP appear resistant to any blood pressure lowering effect of Ca irrespective of NaCl intake.

Animals↗
PubMed1988

Genetic influences on the response to dietary salt reduction, acute salt loading, or salt depletion in humans.

The effect of heredity on blood pressure is established. However, not all genetically predisposed individuals develop an elevated blood pressure. Thus, an environmental factor may also be required for expression of this genetic predisposition. To elucidate this effect further, as well as to examine the relationship between inherited factors and the influence of salt intake, we conducted acute and chronic investigations in normal subjects. We present evidence that renal function, the renin-angiotensin-aldosterone system, and sympathetic nervous system are all influenced by genetic variance. We found that the blood pressure response to both acute changes in volume and changes in salt intake is normally distributed, supporting the notion of salt sensitivity and resistance of blood pressure. We identified phenotypes of haptoglobin as possibly useful indicators of salt sensitivity and resistance. We documented a parent-offspring resemblance in blood pressure and also a maternal-offspring resemblance in the change in blood pressure with salt reduction. We present evidence that suggests that salt-sensitive persons exhibit differences in renin-aldosterone relationships and natriuretic responses consistent with volume expansion compared to salt-resistant individuals. Finally, we identified a potential role for altered adrenoreceptors in the development of salt sensitivity. Our observations speak to the inherited nature of salt sensitivity and resistance of blood pressure. They may have mechanistic implications as well.

Diet, Sodium-Restricted↗
PubMed1987

Influence of genetic variance on sodium sensitivity of blood pressure.

To examine the effect of genetic variance on blood pressure, sodium homeostasis, and its regulatory determinants, we studied 37 pairs of monozygotic twins and 18 pairs of dizygotic twins under conditions of volume expansion and contraction. We found that, in addition to blood pressure and body size, sodium excretion in response to provocative maneuvers, glomerular filtration rate, the renin-angiotensin system, and the sympathetic nervous system are influenced by genetic variance. To elucidate the interaction of genetic factors and an environmental influence, namely, salt intake, we restricted dietary sodium in 44 families of twin children. In addition to a modest decrease in blood pressure, we found heterogeneous responses in blood pressure indicative of sodium sensitivity and resistance which were normally distributed. Strong parent-offspring resemblances were found in baseline blood pressures which persisted when adjustments were made for age and weight. Further, mother-offspring resemblances were observed in the change in blood pressure with sodium restriction. We conclude that the control of sodium homeostasis is heritable and that the change in blood pressure with sodium restriction is familial as well. These data speak to the interaction between the genetic susceptibility to hypertension and environmental influences which may result in its expression.

Adolescent↗
PubMed1987

Effects of age on renal sodium homeostasis and its relevance to sodium sensitivity.

Age-related changes in blood pressure, renal function, and sodium homeostasis suggest that sodium sensitivity of blood pressure may also be influenced by age. Blood pressure was measured in 378 normal volunteers and 198 patients with essential hypertension after an intravenous infusion of normal saline and after sodium and volume depletion. Those whose mean arterial blood pressure decreased more than 10 mm Hg after sodium and volume depletion were considered sodium-sensitive, whereas those with a decrease of less than 5 mm Hg were considered sodium resistant. The normal and hypertensive subjects were divided into groups of those above and those below 40 years of age. The blood pressure responses of both older and younger groups were normally distributed, indicating that blood pressure could either decrease or increase following volume depletion. Older hypertensive and normotensive subjects are more likely to be sodium sensitive. They usually have lower renin values than do younger subjects, but substantial heterogeneity is found. Age and renin status do not reliably predict sodium sensitivity. Volume contraction and dietary sodium restriction are more likely to decrease blood pressure in older than in younger subjects, but regimens must be tailored individually.

Adolescent↗
PubMed1987

Atrial natriuretic factor in sodium-sensitive and sodium-resistant Dahl rats.

We tested the hypothesis that atrial natriuretic factor (ANF) may play a role in the development of hypertension in salt-sensitive Dahl (S) rats as compared to normotensive salt-resistant Dahl (R) rats. We measured immunoreactive ANF in plasma and atria of the inbred (JR) strain of Dahl S and R rats receiving 0.9 or 8% NaCl diets for up to 8 weeks. We also tested the effect of acute volume expansion on plasma and atrial ANF values in rats receiving the 0.9% salt diet. In addition, we examined the effects of exogenous ANF in the form of atriopeptin III given as intravenous bolus infusion at both levels of salt intake. We found no difference in plasma and atrial values between S and R rats irrespective of salt intake. The S and R rats showed a similar, five- to sevenfold increase of plasma ANF in response to acute saline expansion. Finally, we were unable to demonstrate differences between S and R rats in response to atriopeptin III with respect to transient decreases in blood pressure, and pronounced increases in glomerular filtration rate (GFR), renal blood flow or natriuresis. These results do not reveal appreciable changes in the ANF system of Dahl S rats either before or after onset of hypertension when compared to normotensive R rats. Therefore, our findings do not support the notion that ANF is important in the development or maintenance of chronic salt-induced hypertension in S rats.

Anesthesia↗
PubMed1987

Blood pressure, electrolyte and adrenal responses in swim-trained hypertensive rats.

In order to test the effect of aerobic training on blood pressure, and to examine the putative mechanisms involved, stroke-prone spontaneously hypertensive rats (SHR-SP), borderline hypertensive rats (BHR), and Wistar-Kyoto control rats (WKY) were swim-trained for up to 1.5 h twice-daily for 22 weeks. The BHR were F1 back-cross SHR-SP, WKY. A training effect was observed in the trained rats compared to controls, as demonstrated by slower heart rates, heavier hearts and increased cytochrome oxidase activity in their skeletal muscle. Trained SHR-SP and BHR had significantly lower blood pressures at the end of the intervention period (approximately 10 mmHg) compared to controls. Acute increases in blood pressure with swimming were less in trained than in untrained rats. Trained rats had higher extracellular sodium values than untrained rats. Further, trained SHR-SP and BHR had lower intra-erythrocyte sodium values than controls. Increases in corticosterone, epinephrine and norepinephrine with swimming were less in trained rats than in controls. We conclude that exercise conditioning ameliorates hypertension in rats. The mechanism may involve an effect on cation transmembrane transport, as well as decreased, adrenosympathetic tone. Moreover, these effects may be related.

Adaptation, Physiological↗
PubMed1987

Calcium-channel-blocking drugs and renal sodium excretion.

The administration of calcium-blocking drugs exerts a natriuretic response. Acute studies in isolated perfused kidneys and in experimental animals, as well as in man, consistently demonstrate diuresis, natriuresis, calciuresis, and generally kaliuresis, even in the face of arterial blood pressure reduction. Clearance methodology suggests that calcium-blocking drugs exert their natriuretic response by exerting hemodynamic effects, as well as by acting directly on the proximal tubule. Micropuncture studies and experiments utilizing the toad urinary bladder suggest that calcium-blocking drugs impair sodium reabsorption in the distal tubule. Chronic studies in both animals and man, in which sequential urine collections were made in the face of a known sodium intake, corroborate the natriuretic effects of calcium-blocking drugs. Moreover, these studies suggest that the effects of these medications are likely to be clinically important.

Animals↗
PubMed1987

Association of haptoglobin with sodium sensitivity and resistance of blood pressure.

Sodium sensitivity and resistance of blood pressure were examined in 117 normotensive and 85 hypertensive subjects by means of a protocol using rapid extracellular fluid volume expansion with intravenously administered saline (2 L over 4 hours) followed by a day of low dietary sodium intake (10 mEq) and volume contraction induced by a diuretic (furosemide, 120 mg orally). Genetic markers were also examined. Both hypertensive and normotensive subjects with haptoglobin 1-1 phenotype were significantly more (p less than 0.05) likely to be sodium-sensitive than were those with 2-1 or 2-2 phenotypes, and subjects with 2-2 phenotypes were more apt to be sodium-resistant. A second population was examined in which both adults and children with haptoglobin 1-1 phenotype were found to have significantly (p less than 0.05) higher casual systolic and diastolic blood pressures. These two studies independently confirm a relationship between haptoglobin phenotypes and blood pressure and suggest an environmental factor (sodium) as well.

Adolescent↗