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S W Graves

Publications and source records attributed to S W Graves.

At least 37 records · Page 2Linked to original sources
PubMed1997

Sodium pump isoform specificity for the digitalis-like factor isolated from human peritoneal dialysate.

We have isolated a labile, specific sodium pump inhibitor or digitalis-like factor from the peritoneal dialysate of volume-expanded renal failure patients whose levels correlated closely with volume status and blood pressure. This study characterizes the inhibitory profile of this agent compared with that of ouabain against the three alpha-isoforms of the sodium pump. We prepared microsomal Na,K-ATPase from rat tissues representing the highest proportion of one of the alpha-isoforms. Both Northern and Western blot analyses confirmed that kidney had predominantly the alpha1-isoform, skeletal muscle the alpha2-isoform, and fetal brain the alpha3-isoform. Ouabain (5 x 10(-6) mol/L) produced little inhibition of kidney Na,K-ATPase (3.4+/-2.0%) but significant inhibition of skeletal muscle (37.2+/-3.7%, P<.001) and fetal brain (38.8+/-3.5%, P<.001) activity. In contrast, the labile digitalis-like factor, causing comparable inhibition of fetal brain Na,K-ATPase activity (33.3+/-4.7%), produced markedly greater inhibition of kidney (42.5+/-5.6%, P<.001) and moderately greater inhibition of skeletal muscle pump activity (57.7+/-6.3%, P<.05). In addition, the labile digitalis-like factor produced a marked concentration-dependent inhibition of the alpha2- and alpha3-isoforms (r=.79, P=.00005). Experiments combining the labile digitalis-like factor and ouabain confirmed that digitalis-like factor, unlike ouabain, was an effective inhibitor of all three isoforms in rat, in particular alpha2. The different pattern of isoform sensitivity displayed by the labile digitalis-like factor and ouabain further differentiates the two agents and raises some interesting possibilities about the functional implications of the endogenous factor.

Animals↗
PubMed1996

Endogenous sodium pump inhibition: current status and therapeutic opportunities.

One might ask, given the number of false trails that have been pursued, why we, and so many others, have continued to pursue the elusive digitalis-like factor? The answer can be found in the many review articles cited above [4-13]. In animal models of volume-dependent hypertension, evidence favoring sodium pump inhibition as at least a contributing factor, is essentially overwhelming. These observations are supported by multiple lines of less direct evidence in humans which are also compatible with a contribution of a circulating sodium pump inhibitor. Indeed, if multiple premature claims announcing the isolation of the digitalis-like factor had not appeared, this would be one of a large number of interesting scientific areas in which identification of a responsible vector was expected momentarily. The disenchantment so often expressed, we believe, reflects a response to those premature claims. We echo a recent review on the digoxin-like sodium pump inhibitor story from one of the productive groups in this area. "Now that there is little doubt that endogenous digoxin-like inhibitors of sodium transport exist..., the link between these substances, salt intake and vascular tone must be pursued with increasing vigor" [12]. That pursuit, of course, will be easier if the criteria concerning the responsible mediator are employed systematically. Because the current situation resembles so strikingly the situation late in the nineteenth century--when efforts focused on the attempt to identify a specific microorganism as the agent responsible for specific disease--we employed Koch's Postulates as the organizing principle. The challenge faced by Robert Koch over a century ago is identical to the challenge that those of us who are interested in digitalis-like factors face today. Passionate advocacy and equally impassioned denial can be seen as a stage in the scientific process when the problem is important and has proven to be more intractable than anticipated. Substantial, but still circumstantial evidence supports strongly a role for a circulating digitalis-like factor not only in normal sodium homeostasis and in the pathogenesis of salt-sensitive hypertension, but also in the pathogenesis of a wide array of processes that have an uncertain etiology. Although supported by many lines of evidence, this intriguing concept remains controversial, in large part because the responsible factor has proven to be very elusive. Informed opinion today ranges from arguments that the agent does not exist to contrary arguments that the agent has been identified. A very large number of candidates from a wide range of chemical classes have been proposed. Indeed, the large number of candidates, none supported by absolutely definitive evidence, has contributed to the controversy. In this essay, we have attempted to define and illustrate the information that will be required before a candidate becomes widely accepted.

Cardenolides↗
PubMed1996

Reversal of sodium pump inhibitor induced vascular smooth muscle contraction with digibind. Stoichiometry and its implications.

The possibility that a circulating sodium pump inhibitor contributes to the pathogenesis of volume-dependent hypertension via an action on vascular smooth muscle (VSM) is supported by multiple lines of investigation, but remains controversial. We had two goals in this study. The first was to compare the pattern of contractile response of rabbit aorta induced by two candidates, ouabain and a labile sodium pump inhibitor that we have identified in the peritoneal dialysate of volume-expanded hypertensive patients with chronic renal failure. Our second goal was to examine the ability of Digibind, a Fab fragment of antisera directed against digoxin, to reverse VSM contraction induced by both agents. Ouabain induced a concentration-dependent contraction, which was delayed in onset, was gradual, and reached a stable plateau after many hours. The labile sodium pump inhibitor induced a qualitatively similar series of responses. Digibind rapidly reversed the contractile responses to both sodium pump inhibitors, with a rate of relaxation that matched that induced by physical removal of the pump inhibitor from the bath. For ouabain, the Digibind:ouabain stoichiometry was highly predictable. When Digibind was present in a molar concentration equivalent to that of ouabain, or less, it had no effect. When the Digibind concentration was twice that of ouabain, complete relaxation occurred. Although the concentration:VSM response relationship for ouabain was steep, the concentration:effect interaction with Digibind was even more steep. The molar concentration of Digibind required to reverse the effects of the labile endogenous inhibitor from peritoneal dialysate was consistently lower than that for ouabain, which is compatible with either greater potency of the labile factor in VSM or greater affinity for Digibind. These findings are compatible with a role for one or more endogenous sodium pump inhibitors as the determinant of vascular smooth muscle tone in the volume-sensitive hypertension of renal disease.

Animals↗
PubMed1996

A new interference in some digoxin assays: anti-murine heterophilic antibodies.

BACKGROUND: We describe a patient with cirrhotic liver disease and atrial fibrillation who was treated with spironolactone and digoxin. He was hospitalized because of an incidental finding of a high serum digoxin level (4.2 micrograms/L), but he remained asymptomatic without emerging arrhythmias. Despite discontinuation of both drugs, his serum digoxin level persisted at or above 3.0 micrograms/L for approximately 5 weeks, drawing into question the accuracy of the digoxin assay. METHODS: Additional digoxin methods gave lower, discrepant results, providing evidence of an assay interference, and several possible sources of digoxin false positivity were evaluated. This included assessment of the contribution of digoxin-like immunoreactive factor (DLIF), digoxin metabolites, and spironolactone. Because the routine digoxin assay used a monoclonal antibody, we also tested for another hypothetical interference: human heterophilic ("anti-mouse") antibodies. RESULTS: We found no contribution from DLIF, digoxin antibodies, or spironolactone to the apparent digoxin results. However, the use of protein A to complex and selectively remove immunoglobulin G molecules markedly lowered the apparent digoxin value, as did the less specific process of ultrafiltration. CONCLUSIONS: These results suggest a previously unreported cause of digoxin false positivity: heterophilic antibodies, which have been reported to bind murine monoclonal antibodies in other assays. Because newer digoxin assays now use murine monoclonal antibodies, the possible presence of heterophilic, anti-mouse antibodies should now be considered in the interpretation of a high digoxin level.

Anti-Arrhythmia Agents↗
PubMed1996

Specificity of the volume-sensitive sodium pump inhibitor isolated from human peritoneal dialysate in chronic renal failure.

Compromised renal function predisposes to volume-dependent hypertension. Increased plasma levels of a sodium pump inhibitor as a possible pathogenetic factor have been demonstrated by many investigators in such patients, but efforts to identify the responsible agent have led to many, diverse candidates. Our premise in this study is that candidacy must depend on the satisfaction of rigorous criteria, including a specific action of the agent on the sodium pump. These criteria included reversibility, concentration dependence, receptor mediation, and an action at the appropriate step in the enzyme cycle. These criteria were applied to a potent [Na,K]ATPase inhibitor we have identified in the peritoneal dialysate of patients with chronic renal failure, present only during extracellular fluid volume expansion, the levels of which are correlated with the blood pressure rise that results from excessive NaCl and water intake. In microsomes that contained both [Na,K]ATPase and other ATPases, this candidate inhibited only the Na and K dependent, ouabain-sensitive ATPase. It displaced ouabain from the cardioglycoside binding site and its binding was linked to inhibition. Inhibition was produced by slowing the pump's dephosphorylation step, the exact action of all cardioglycosides. Finally, the candidate cross reacted with a digoxin Fab fragment and this Fab reversed its inhibition of [Na,K]ATPase. Together, these experiments demonstrate that the PD candidate specifically, and reversibly, inhibits the sodium pump via the cardioglycoside binding site, and hence, meets this crucial criterion for candidacy.

Antineoplastic Agents↗
PubMed1996

Elemental composition of Na pump inhibited rabbit aorta VSM cells by electron probe X-ray microanalysis.

The Na pump in vascular smooth muscle (VSM) is likely to influence not only intracellular Na content but also the content and distribution of other cations and anions measured by electron probe X-ray microanalysis (EPXMA). The hypothesis we tested was that EPXMA of pump-inhibited VSM would yield a characteristic cellular elemental profile, providing insight into the contribution of the Na pump to the intracellular milieu and an approach to identifying when VSM operates under the constraints of pump inhibition. We assessed the contractile state and elemental EPXMA profile of rabbit aorta that was either quiescent or contracted by serotonin (10(-6) M) or ouabain (10(-6) M). VSM cytoplasm showed the anticipated low Na (28 +/- 2 mM) and high K (182 +/- 5 mM) content. With ouabain, Na rose and K fell to reverse the Na-to-K ratio (0.15 +/- 0.01 vs. 6.6 +/- 0.3; P < 0.01). With serotonin, the ratio rose slightly (0.28 +/- 0.2; P < 0.05). Nuclei and mitochondria showed a similar pattern. CI showed a small increase (56 +/- 2 to 102 +/- 4 mM) with ouabain, a shift that could not be accounted for on the basis of charge redistribution to maintain neutrality because the change in Na and K were essentially offsetting. EPXMA measures total and not ionized Ca. If changes in cytoplasmic Ca occurred, they were too small to be measured by the imaging methods employed. The sustained, myogenic contractile response of VSM to Na pump inhibition shows a characteristic elemental profile that could prove useful in its identification. Direct measurement of membrane potential during the myogenic response to Na pump inhibition should have a high priority.

Animals↗
PubMed1995

Determination of methyleugenol in rodent plasma by high-performance liquid chromatography.

A method has been developed and validated for the analysis of methyleugenol, a volatile flavoring agent, in rodent plasma at concentrations from 0.050 to 10.0 micrograms/ml. The method involves the addition of acetonitrile to the plasma, removal of the protein precipitate, and analysis of the supernatant by reversed-phase (C18) HPLC using an acetonitrile-water mixture with UV detection. The precision, accuracy, sensitivity, and specificity of the method were assessed. The stability of methyleugenol in plasma, during freeze-thaw cycles, refrigerated at the extract stage, and during the analysis was evaluated. The recovery of methyleugenol from plasma was also determined. This method was found to be acceptable for plasma concentrations in toxicokinetic studies of methyleugenol in rodents. Over 400 samples from toxicokinetic studies have been successfully analyzed to date. Kinetic data from a preliminary single administration intravenous and oral study in rats is also presented.

Acetonitriles↗
PubMed1995

Digitalis-like factor and digoxin-like immunoreactive factor in diabetic women with preeclampsia, transient hypertension of pregnancy, and normotensive pregnancy.

An endogenous sodium pump inhibitor, or digitalis-like factor (DLF), has been postulated to mediate essential hypertension. It may also play a role in preeclampsia. However, studies of this factor in hypertensive pregnancy have not provided consistent findings. Part of this may be due to the absence of subclassification of pregnant women with pregnancy-induced hypertension (PIH) when assessing these parameters. In this study we explored serum DLF and digoxin-like immunoreactive factor (DLIF) in insulin-dependent diabetic (IDDM) women with normotensive pregnancies or PIH, comparing them to each other and to nondiabetic pregnant women. Our results demonstrated that nondiabetic women with preeclampsia (PE, PIH with proteinuria) had significantly increased serum DLF and DLIF compared to normotensive pregnant women (NL BP). Women with transient hypertension of pregnancy (THP, PIH without proteinuria) had intermediate values (DLF. NL BP: 3.3 +/- 0.6, THP: 4.8 +/- 1.1, PE: 7.6 +/- 1.3% inhibition [Na,K]-ATPase, P < .05 ANOVA; DLIF. NL BP: 0.22 +/- 0.02, THP: 0.28 +/- 0.03, PE: 0.35 +/- 0.02 ng digoxin equivalents/mL, P < .05 ANOVA). Pregnant normotensive IDDM women had significantly higher serum DLF and DLIF activity than their nondiabetic counterparts (DLF. non-IDDM NL BP: 3.3 +/- 0.6 v IDDM NL BP: 8.8 +/- 1.2% inhibition [Na,K]-ATPase, P = .0008; DLIF. non-IDDM NL BP: 0.22 +/- 0.02 v IDDM NL BP: 0.31 +/- 0.02 ng digoxin equivalents/mL, P = .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Volume sensitive hypertension and the digoxin-like factor. Reversal by a Fab directed against digoxin in DOCA-salt hypertensive rats.

Although volume and vasoconstriction have been considered polar elements in a useful pathogenetic hypertension model, many observations suggest that vasoconstriction is involved in volume-dependent hypertension, reflecting the effect of a digitalis-like factor. To examine that possibility, we assessed the depressor responses to Digibind, an antibody Fab directed against digoxin, in a volume-dependent model--DOCA-salt-induced hypertension in rats. Digibind (10 mg/kg, intravenously) induced a gradual blood pressure fall over 2 h that was sustained for 4 h (P < .001). Blood pressure did not fall with Digibind when DOCA was administered without salt or a high-salt intake was provided without DOCA. The intracellular sodium content of the rat aorta, measured by atomic absorption spectroscopy after cold choline wash, was increased in the DOCA-high-salt rats (23.3 +/- 2.7 mEq/L) compared to control rats (12.1 +/- 0.8 mEq/L; P < .001). Aorta sodium content, in parallel with blood pressure, was not increased either by dietary salt supplementation without DOCA, or by DOCA with a low-salt diet. Sodium pump activity was measured as 86Rb uptake into vascular smooth muscle (VSM). Both ouabain-sensitive and ouabain-resistant 86Rb uptake were significantly higher in VSM from DOCA-high-salt animals (P < .01). Despite its effectiveness in reducing blood pressure in this model, Digibind influenced neither VSM sodium content nor 86Rb uptake. The results are consistent with a role for a circulating digitalis-like factor in this volume-dependent model, but events at the VSM level are complex.

Animals↗
PubMed1995

A sensitive [Na,K]ATPase assay specific for inhibitors acting through the digitalis-binding site.

Efforts to study the endogenous sodium pump inhibitor (ESPI) have been complicated by the limited specificity of available assays. We recently developed an assay of [Na,K]ATPase inhibition more sensitive than conventional assays. This enhancement reflects a prereaction step that increases binding affinity of digitalislike molecules to the digitalis receptor. We tested the possibility that this enhanced inhibition is limited to inhibitors acting specifically through the digitalis-binding site. Using both the standard and sensitive [Na,K]ATPase methods, known specific inhibitors of the sodium pump (ouabain, digoxin, bufalin) showed significant increases in the inhibition in the sensitive as compared with the standard [Na,K]ATPase assay (ouabain 34.4 +/- 7.3 vs. 8.3 +/- 0.5%, digoxin 43.2 +/- 9.1 vs. 7.2 +/- 3.1%, bufalin 46.9 +/- 5.0 vs. 22.6 +/- 1.6%). Some proposed candidates for the ESPI, acknowledged to be nonspecific inhibitors, showed no enhancement (oleic acid 36.0 +/- 4.5 vs. 34.8 +/- 5.6%, lysophosphatidyl choline 10.8 +/- 3.5 vs. 12.8 +/- 5.2%, and vanadate 34.3 +/- 8.8 vs. 33.8 +/- 1.4%). Other candidates, whose inhibitory specificity is unknown, including an ESPI from the peritoneal dialysate of patients with renal failure were also studied. The ESPI showed enhanced inhibition (24.1 +/- 4.9 vs. 5.3 +/- 2.0%). These studies suggest that the sensitive assay in conjunction with a standard [Na,K]ATPase assay may allow the early determination of candidates interacting specifically with the digitalis receptor to inhibit the sodium pump.

Animals↗
PubMed1995

Koch's postulates and the digitalis-like factor.

Substantial, but still circumstantial evidence, supports strongly a role for a circulating digitalis-like factor in the pathogenesis of salt-sensitive hypertension. Although supported by many lines of evidence, this intriguing concept remains controversial, in large part because the responsible factor has proven to be very elusive. A very large number of candidates from a wide range of chemical classes have been proposed. Indeed, the large number of candidates, none supported by absolutely definitive evidence, has contributed to the controversy. In this essay, we have attempted to define the information that will be required before a candidate becomes widely accepted. Because the current situation resembles so strikingly the situation late in the nineteenth century--when efforts focused on the attempt to identify a specific micro-organism as the agent responsible for specific disease--we employed Koch's postulates as the organizing principle. The challenge faced by Robert Koch over a century ago is identical to the challenge that we face today.

Blood Proteins↗
PubMed1994

Sustained volume expansion and [Na,K]ATPase inhibition in chronic renal failure.

Hypotheses regarding the pathogenesis of volume-dependent hypertension have invoked an endogenous sodium pump inhibitor or digitalis-like factor (DLF) to link altered sodium homeostasis to the rise in blood pressure. Our goal was to develop a clinical protocol that achieved predictable, sustained volume expansion, with the premise that renal failure patients on peritoneal dialysis would increase intravascular volume, gain weight, and raise blood pressure (BP) in relation to measured increases in DLF. In a 5-day protocol, dialysis was kept constant but dietary NaCl and fluids were modified in 7 patients. DLF was measured as inhibition of [Na,K]ATPase. Likewise, the first 2 L of daily peritoneal dialysate (PD) was processed on HPLC and the eluate analyzed for DLF. The group achieved significant weight gain (WT) by day 3 (delta WT = 4.1 +/- 1.2 kg, P < .05). Likewise, mean arterial pressure (MAP) and plasma DLF activity increased significantly. All variables were highly correlated (DLF v WT: R = 0.88, P = .004; MAP v DLF: R = 0.82, P = .01; MAP v WT: R = 0.90, P = .003). Although a number of HPLC fractions contained agents that interacted with the assay, only one PD HPLC fraction (at 19.5 min) contained DLF activity that correlated with changes in MAP (R = 0.60, P = .002), and body weight (R = 0.67, P = .0003). We conclude that candidate DLF responds to sustained volume expansion and the relationship suggests that it could influence blood pressure. Moreover, the application of stringent criteria to the confusing array of factors in plasma that may affect assays for DLF appears to reduce the field dramatically, to a single candidate in this setting.

Adult↗
PubMed1994

The sodium pump in hypertension.

There is increasing evidence that the sodium pump plays a role in essential hypertension. Recent publications have focused on intrinsic alterations in pump activity, external modification of pump activity by circulating inhibitors, and endothelial mediation of endogenous inhibitor effects on the vascular response. Hence, this review focuses on these areas. Although there is intriguing evidence that alterations in sodium pump activity might contribute to the pathogenesis of hypertension, in at least some sodium-sensitive models and some patients with essential hypertension, the evidence remains circumstantial and areas of substantial controversy exist.

Animals↗
PubMed1994

Corticotrophin releasing hormone levels in human plasma and amniotic fluid during gestation.

OBJECTIVE: Corticotrophin releasing hormone, a hypothalamic neuropeptide also made in placenta, may regulate fetal maturation in a stress-responsive manner. The objectives of this study were: (1) to determine if levels of corticotrophin releasing hormone in the amniotic fluid correlate with fetal lung maturation; (2) to confirm that third trimester plasma levels of corticotrophin releasing hormone are increased in patients with pregnancy-induced hypertension compared to normotensives, and (3) to increase the recovery of extracted corticotrophin releasing hormone from plasma and amniotic fluid. DESIGN: (1) Levels of corticotrophin releasing hormone in amniotic fluid during the third trimester were compared with those of saturated phosphatidyl choline. (2) Corticotrophin releasing hormone levels were measured in a group of normotensive pregnant women during the entire gestation period. Corticotrophin releasing hormone levels during the third trimester were compared in normotensives and patients with pregnancy-induced hypertension. PATIENTS: Twenty-one non-pregnant normal volunteers and 63 pregnant women. MEASUREMENTS: Blood pressure, corticotrophin releasing hormone in plasma and amniotic fluid, and saturated phosphatidyl choline in amniotic fluid. RESULTS: Corticotrophin releasing hormone levels in amniotic fluid samples during the third trimester ranged from 12 to 98 pmol/l and positively correlated with the saturated phosphatidyl choline levels, but not with gestational age. A significant difference existed in plasma corticotrophin releasing hormone concentration between gestational age-matched third trimester normotensive and hypertensive gravids: corticotrophin releasing hormone levels were significantly lower in normotensives (223 +/- 65 pmol/l) than in patients with pregnancy-induced hypertension (544 +/- 106 pmol/l, P = 0.001). Plasma corticotrophin releasing hormone increased with gestational age from 51 pmol/l (range 8.4-85) at 25-32 weeks to 375 pmol/l (range 35-1386) at 33-40 weeks. During the third trimester the rise in plasma corticotrophin releasing hormone conformed to an exponential mathematical model of a positive feedback loop between placental corticotrophin releasing hormone and fetal adrenal cortisol. CONCLUSIONS: During the third trimester of pregnancy there is a positive correlation between the level of amniotic fluid corticotrophin releasing hormone and that of saturated phosphatidyl choline. The positive correlation between amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl choline, but not between amniotic fluid corticotrophin releasing hormone and gestational age, suggests that a factor(s), such as stress, may affect both amniotic fluid corticotrophin releasing hormone and saturated phosphatidyl choline in parallel. Furthermore, our data are consistent with the hypothesis that the rise in placental corticotrophin releasing hormone is coupled to an increase in fetal glucocorticoid and lung maturation, and that stresses such as pregnancy-induced hypertension may accelerate this process.

Amniotic Fluid↗
PubMed1994

[Ca2+]i signaling in pregnant human myometrium.

The purpose of the present study was to determine the changes in intracellular ionized calcium concentration ([Ca2+]i) or [Ca2+]i sensitivity accompanying spontaneous and agonist-induced contraction of human myometrium at term pregnancy, as well as to quantify the response to three prototypical agonists: 1) oxytocin, 2) vasopressin, and 3) phenylephrine. Uterine biopsies were obtained at the time of cesarean section from patients who delivered at or near full-term gestation. These preparations were used to measure isometric force development and [Ca2+]i levels with the luminescent calcium indicator aequorin. Concentration-response relationships were determined with respect to isometric force development in the presence of the agonist. [Ca2+]i-force relationships were determined with respect to spontaneous phasic contractions, as well as agonist-induced phasic and tonic contractions. The results provide evidence that the phasic nature of term human myometrium is due to 1) the resting [Ca2+]i level being less than the calcium threshold for contractions and 2) the inability of the tissue to maintain high [Ca2+]i levels for prolonged periods of time. In addition, calcium-independent mechanisms of regulation were suggested by the relatively minor calcium sensitizing action of oxytocin and the observation that relaxation of tonic contractions preceded the fall in [Ca2+]i levels.

Calcium↗
PubMed1994

Glucose intolerance as a predictor of hypertension in pregnancy.

Insulin resistance is associated with and may be causal in essential hypertension, but the relation between insulin resistance and hypertension arising de novo in pregnancy is unclear. Transient hypertension of pregnancy (new-onset nonproteinuric hypertension of late pregnancy) is associated with a high risk of later essential hypertension and thus may have similar pathophysiology. To assess the association between glucose intolerance and subsequent development of proteinuric and nonproteinuric hypertension in pregnancy in women without underlying essential hypertension or overt glucose intolerance, we performed a retrospective case-control study comparing glucose levels on routine screening for gestational diabetes mellitus among women subsequently developing hypertension. Women who developed hypertension in pregnancy (n = 97) had significantly higher glucose levels on 50-g oral glucose loading test (P < .01) and a significantly higher frequency of abnormal glucose loading tests (> or = 7.8 mmol/L) (P < .01) than women who remained normotensive (n = 77). Relative glucose intolerance was particularly common in women who developed nonproteinuric hypertension. Women who developed hypertension also had greater prepregnancy body mass index (P < or = .0001) and baseline systolic and diastolic blood pressures (P < or = .0001 for both), although all subjects were normotensive at baseline by study design. However, after adjustment for these and other potential confounders, an abnormal glucose loading test remained a significant predictor of development of hypertension (P < .05) and, specifically, nonproteinuric hypertension in pregnancy (P < .01). Among a subgroup of women in whom insulin levels were also measured (n = 80), there was a nonsignificant trend toward higher insulin levels in women developing hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗