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Biomedical subjects

F C Luft

Publications and source records attributed to F C Luft.

At least 613 records · Page 34Linked to original sources
PubMedDate not supplied

Pituitary adenylate-cyclase-activating peptides relax human coronary arteries by activating K(ATP) and K(Ca) channels in smooth muscle cells.

Pituitary adenylate-cyclase-activating peptides (PACAPs) are potent dilators of arteries, including human coronary arteries. We tested the importance of specific K+ channel regulatory mechanisms in human arterial smooth muscle relaxation induced by PACAPs, using contraction and patch clamp measurements on human coronary artery vascular smooth muscle cells. PACAP27 and PACAP38 produced dose-dependent relaxations of 5 microM PGF2alpha-preconstricted rings, with half-maximal relaxations at 1.0 nM and 2.0 nM, respectively. Both peptides induced complete relaxation at 100 nM. Pretreatment of the vessels with the ATP-dependent K+ (K(ATP)) channel blocker glibenclamide (1 microM) or with the Ca2+-activated K+ (K(Ca)) channel blocker iberiotoxin (100 nM) inhibited PACAP27-induced relaxation in an additive manner. Moreover, in the patch clamp experiments on freshly isolated cells from human coronary arteries, PACAP27 (100 nM) induced a large, nonrectifying, outward (I(K)(ATP)) K+ current in a proportion of cells and a voltage-dependent outward (I(K)(Ca)) K+ current in other cells. The PACAP27-induced I(K)(ATP) was blocked by glibenclamide (3 microM), while the PACAP27-stimulated I(K)(Ca) was blocked by iberiotoxin (100 nM). These findings provide the first evidence that relaxation of arterial smooth muscle cells by PACAPs is mediated by opening of K(ATP) and K(Ca) channels. The data indicate that both K(ATP) and K(Ca) channels in vascular smooth muscle cells may serve as final common pathway to induce vasorelaxation by endogenous vasoactive signals in man.

Coronary Vessels↗
PubMedDate not supplied

Genetic influences on renin, aldosterone, and the renal excretion of sodium and potassium following volume expansion and contraction in normal man.

To investigate the influence of hereditary on plasma renin activity (PRA), plasma aldosterone concentrations (PAC), blood pressure, and the renal excretion of sodium and potassium following volume expansion and contraction in normal man, we studied 37 pairs of monozygotic (MZ) and 18 pairs of dizygotic (DZ) twins. Volume expansion was achieved by the intravenous infusion of 2L normal saline; volume contraction was accomplished by a low-sodium diet and 120 mg oral furosemide. The presence of genetic variance was tested by calculating the within pair and among component estimates of genetic variance. Outpatient 24-hour-urine collections suggested that MZ and DZ twins ingested diets similar in sodium and potassium content, and failed to reveal genetic influences on the dietary preferences for these electrolytes. The PRA values suggested heritable influences during both the volume expanded and contracted state with the added stimulus of upright posture. Heritable influences were observed on PAC and were most apparent in the basal state on the day of volume expansion. An influence of heredity on blood pressure was most apparent during volume contraction. Urinary sodium excretion (UNaV), urinary potassium excretion (UKV), fractional excretion of sodium (FENa), and fractional excretion of potassium (FEK) revealed evidence of significant genetic variance under the condition of volume expansion. in that state, systolic blood pressure was directly correlated with PRA, PAC, and inversely with FENa. The data suggest that the renal regulation of sodium and potassium excretion is in part influenced by heritable factors that may in turn contribute to the development of hypertension in some individuals.

Adolescent↗
PubMedDate not supplied

Norepinephrine in urine and plasma following provocative maneuvers in normal and hypertensive subjects.

Urinary norepinephrine (UNE) excretion rate and venous plasma norepinephrine (PNE) concentrations were studied in 266 normotensive and 107 essential hypertensive men and women under conditions of volume expansion with 2 liters of intravenous normal saline over 4 hours, and volume contraction with a 10 mEq sodium diet and 120 mg oral furosemide. The UNE excretion rate was correlated with age in normal women only. In men, and in hypertensives of both sexes, the relationship appeared to be biphasic. The PNE concentration was not correlated with age in the hypertensive subjects. Insufficient numbers of older subjects were available to exclude absolutely such a relationship among normals. The UNE and PNE were influenced by volume expansion and contraction in both normals and hypertensives; however, normals exhibited a correlation between UNE and blood pressure as well as consistent correlations between UNE and PNE, neither of which were observed in the hypertensives. Hypertensive women generally had greater UNE and PNE values than normal women or hypertensive men. Hypertensive women may have altered sympathetic activity.

Adult↗
PubMedDate not supplied

An approach to the evaluation of genetic influences on factors that regulate arterial blood pressure in man.

To assess the influence of heredity on factors that help regulate the arterial blood pressure in man, we conducted sodium-loading and depletion studies in monozygotic and dizygotic twins, normotensive first-degree relatives of essential hypertensives, and in normotensive control subjects matched for age, sex, and race. Following sodium-loading, we found evidence for the influence of genetic variance on the natriuretic responses, plasma renin activity (PRA), plasma aldosterone concentrations (PA), and plasma and urinary norepinephrine. Relatives of hypertensives differed from controls in that they had higher blood pressures, greater renin values, and relatively sluggish natriuretic responses. Since renin and fractional sodium excretion values were inversely correlated in all subject groups, it is possible that the heritable influences we observed on sodium excretion were mediated by the renin-angiotensin-aldosterone system.

Adolescent↗
PubMedDate not supplied

The glomerular filtration barrier in the spontaneously hypertensive rat.

To determine whether the differences in the physiological characteristics of SHR and WKY kidneys might be related to differences in renal structure, we studied the kidneys of SHR and WKY rats utilizing scanning and transmission electron microscopy and latex perfusion of the glomerular vasculature. Scanning and transmission electron microscopy revealed a smaller diameter in the glomerular endothelial fenestrae of SHR compared to that in WKY rats even prior to the development of differences in blood pressure. With age, the density and diameter of SHR endothelial fenestrae progressively decreased, which was not true in WKY rats. Latex casts of glomerular vasculature showed the frequent presence of afferent arteriolar constriction in 12-week-old SHR. Thus, the filtration barrier of the SHR is abnormal. THe pathogenesis of hypertension in the SHR is complex and probably multifactorial; however, renal structural changes may contribute to the development and maintenance of hypertension. The afferent arteriolar constrictions may be the structural basis for the increased vascular resistance described in the SHR.

Animals↗
PubMedDate not supplied

Sodium intake alters the effects of norepinephrine on blood pressure.

To examine the interactions between sodium balance and the sympathetic nervous system, we studied eight normotensive men after high (800 mEq/day) and low (10 mEq/day) sodium intake. We measured blood pressure (BP), arterial, venous, and urinary norepinephrine (NE) before and during incremental infusion of NE. We found significant direct, linear relationships (p less than 0.001) between the dose of NE infused and arterial and venous NE levels, and with mean arterial BP at both levels of sodium balance. In addition. the sensitivity was greater and the threshold of pressor response to NE as well as the basal concentrations of NE in arterial and venous plasma significantly lower (p less than 0.05) after the high sodium period. These observations expose heretofore unrecognized qualitative and quantitative interactions between sodium balance and NE that are capable of influencing BP in man.

Adult↗
PubMedDate not supplied

Overnight urine collections to estimate sodium intake.

This study was undertaken to formulate reliable confidence limits for the relationship between nocturnal and 24-hour urine sodium (Na) excretion for use in population compliance studies. Urine excretions were measured in 12 white and 12 black men at three levels of sodium (Na) intake (10, 200, and 400 mEq/day) for 7 days. Nocturnal Na, chloride (Cl), and Cl determined by titrator stick were all highly correlated (r greater than or equal to 0.86, p less than 0.001) with 24-hour UNaV. No significant difference could be attributed to race. Discriminate analysis revealed that the subjects could be categorized with respect to Na intake with accuracies of 95%, 90%, and 85% (low, middle, and high Na intake respectively) by means of two nocturnal urine Cl titrator stick measurements. In addition, two such measurements showing nocturnal UClV less than 10 mEq indicated with 95% accuracy that 24-hour UNaV was less than 60 mEq. According to these data, measurement of nocturnal Na or Cl excretion is a useful means of assessing compliance to a low sodium intake, and the titrator sticks are a convenient and inexpensive tool.

Adult↗
PubMedDate not supplied

Sodium intake and essential hypertension.

This review briefly considers the hypothesis that a generous dietary sodium intake contributes to the development or maintenance of essential hypertension. Three lines of evidence are presented that are not mutually exclusive. Epidemiological studies examining sodium intake, prevalence of hypertension, and increases of blood pressure with age provide circumstantial support for the concept that hypertension is related to sodium intake. Analyses of cellular electrolyte transport suggest that hypertensives and their relatives are at a disadvantage with respect to extruding sodium from cells. A conceptual framework indicates that blood pressure is determined by a balance between the natriuretic effect of increased blood pressure and the pressor effect of sodium retention. Clinical studies in humans support the sodium hypothesis. The kidney's ability to excrete sodium and its sodium regulatory system are genetically determined. In hypertensive humans, blood pressure is directly correlated with total body and exchangeable sodium, a relationship that increases with age. Groups at risk for hypertension excrete sodium less well then those at less risk. Yet both hypertensives and normotensives exhibit heterogeneous blood pressure responses when sodium-loaded or -depleted. It has not been shown that sodium restriction will prevent the development of hypertension in normal individuals; however, it is clear that sodium restriction is an important aspect of management. In three prospective randomized controlled trials, practical sodium restriction lowered blood pressure by 8 mm Hg. Such a decrease would lower cardiovascular morbidity by 10% to 15%. Were means available to detect "salt-sensitive" hypertensives, sodium restriction could be conducted in a more appropriate fashion.

Adult↗
PubMedDate not supplied

Estimating dietary sodium intake in individuals receiving a randomly fluctuating intake.

Previous investigations examining techniques to estimate sodium intake in free-living persons failed to consider a varying intake or were not conducted under circumstances in which the intake was actually known. To examine the utility of 24-hour and nocturnal urine collections as estimation of sodium intake under such conditions, we studied 43 white and black men and women ingesting a known sodium intake for 10 days that was randomly varied daily, with a mean intake of 150 mEq/day + 2 SD (range, 50 to 250 mEq/day). The mean 24-hour sodium excretion (UNaV) per day was and 24-hour UNaV estimated that day's sodium intake accurately for the entire 10 days, the average of several 24-hour collections was required. Nine collections were optimal (r = 0.75). Nocturnal specimens were not helpful; the average of all 10 collections correlated weakly (r = 0.30) with sodium intake. These data suggest that to estimate mean sodium intake accurately in free-living persons, only 24-hour collections are useful, although nocturnal collections are helpful in evaluating compliance with low sodium intake.

Adult↗
PubMedDate not supplied

Renal afferent arteriole in the spontaneously hypertensive rat.

We conducted morphometric studies on the afferent arteriole of spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats to gain a better understanding of its changes with the development of hypertension. Differences may be related to the SHRs' increased renal vascular resistance. Methacrylate vascular casts were made of the renal vasculature after perfusion fixation with glutaraldehyde. These vascular casts were then examined and measurements made with the scanning electron microscope. Results from this examination of the scanning electron microscope demonstrated a smaller afferent arteriolar diameter in the SHR, compared to the WKY, for both the inner and outer cortical glomeruli. This difference was seen in the 6-week-old SHR, prior to a statistically different blood pressure from the WKY controls, as well as in the 12-week-old hypertensive SHR. However, this afferent diameter difference between rat strains was more pronounced in rats at 12 weeks of age. The tapering of the afferent arteriole (difference between proximal and distal afferent diameters) was greater in the 12-week-old SHR than in the age-matched WKY or 6-week-old SHR. We conclude that the smaller caliber afferent arterioles of the SHR may predispose and play a role in the pathogenesis of the subsequent hypertension. The increased afferent arteriolar tapering seen in the hypertensive SHR relates to the already present increased blood pressure. Wall thickness/radius ratios are not different between rat strains (SHR and WKY) at either 6 or 12 weeks of age. These results suggest increased vascular constriction or hypoplastic vessels as the cause of the smaller caliber vessels in the SHR rather than increased wall thickness.

Animals↗
PubMedDate not supplied

Local angiotensin II generation in the rat heart: role of renin uptake.

To elucidate the local effects of renin in the coronary circulation, we examined local angiotensin (Ang) I and II formation, as well as coronary vasoconstriction in response to renin administration, and compared the effects with exogenous infused Ang I. We perfused isolated hearts from rats overexpressing the human angiotensinogen gene in a Langendorff preparation and measured the hemodynamic effects and the released products. We also investigated cardiac Ang I conversion, including the contribution of non-angiotensin-converting enzyme-dependent Ang II-generating pathways. Finally, we studied Ang I conversion in vitro in heart homogenates. Renin and Ang I infusion both generated Ang II. Ang II release and vasoconstriction continued after renin infusion was stopped, even though renin disappeared immediately from the perfusate. In contrast, after Ang I infusion, Ang II release and coronary flow returned to basal levels. Ang I conversion (Ang II/Ang I ratio) was higher after renin infusion (0.109+/-0.027 versus 0.026+/-0.003, 15 minutes, P<.02) compared with infused Ang I. Remikiren added to the renin infusion abolished Ang I and II; captopril suppressed only Ang II, whereas an AT1 receptor blocker did not affect Ang I and II formation. All the drugs prevented renin-induced coronary flow changes. Total cardiac Ang II-forming activity was only partially inhibited by cilazaprilat (4.1+/-0.1 fmol x min(-1) x mg[-1]) and on a larger extent by chymostatin (2.6+/-0.3 fmol x min(-1) x mg[-1]) compared with control values (5.6+/-0.4 fmol x min(-1) x mg[-1]). We conclude that renin can be taken up by cardiac or coronary vascular tissue and induces long-lasting local Ang II generation and vasoconstriction. Locally formed Ang I was converted more effectively than infused Ang I. Furthermore, the comparison of in vivo and in vitro Ang I conversion suggests that in vitro assays may underestimate the functional contribution of angiotensin-converting enzyme to intracardiac Ang II formation.

Angiotensin I↗
PubMedDate not supplied

Calcium channel blockade with nitrendipine. Effects on sodium homeostasis, the renin-angiotensin system, and the sympathetic nervous system in humans.

To test the hypothesis that the antihypertensive effect of the calcium channel blocking drug nitrendipine is in part related to natriuresis, we gave 16 subjects (8 normal, 8 hypertensive) placebo for 8 days followed by nitrendipine titrated to 20 mg twice daily for 8 days. The same diet was prepared for each meal for the entire study. Sodium intake was fixed for each subject and averaged 150 mEq/day. All urine was collected every day. Blood was drawn at the end of the placebo and nitrendipine periods for renin, aldosterone, and norepinephrine values. Nitrendipine caused a significant increase (p less than 0.05) in cumulative sodium excretion of 161 mEq over 7 days in the normal subjects and 103 mEq in hypertensive subjects. Potassium excretion was unaffected. In both hypertensive and normal subjects, plasma renin and plasma norepinephrine activity increased significantly (p less than 0.05), while plasma aldosterone levels did not change. Upright systolic blood pressure decreased significantly (p less than 0.05) in both groups, whereas upright diastolic blood pressure decreased only in hypertensive subjects. We conclude that blood pressure lowering effects of this drug may be in part related to natriuresis and that calcium channel blockade may dissociate plasma renin activity from that of aldosterone.

Adult↗
PubMedDate not supplied

The use of exchange transfusions: a potentially useful adjunct in the treatment of fulminant falciparum malaria.

Fulminant falciparum malaria with greater than 500,000/mm3 parasites in the peripheral blood portends a poor prognosis. We recently managed a patient who had greater than 1.2 million/mm3 parasitized erythrocytes in her peripheral blood, following initially inadequate antimalarial therapy, with exchange transfusion in addition to conventional chemotherapy. This patient recovered from her disease despite severe cerebral involvement and acute failure. We feel that exchange transfusion was a useful adjunct and should be considered in patients with life threatening falciparum malaria when conventional measures fail to control the disease.

Adult↗
PubMedDate not supplied

Echocardiography in the diagnosis of pericarditis in patients with uremia.

Uremic pericarditis occurred in 39 uremic patients who were treated in our program during a 4 yr period. The diagnosis was considered, but could not be established, in an additional 55 patients. A presumptive etiology remediable to a specific plan of treatment was identified in 9 patients who developed pericarditis following the initiation of dialysis. Uremic pericarditis occurring in patients who had yet been dialyzed, regularly responded to aggressive dialysis treatment. Echocardiography was the single, most important test to evaluate patients with suspected pericarditis. Limited pericardiectomy was safe and effective treatment in those patients not responding to conservative management.

Echocardiography↗