New 3-hydroxyflavanone (dihydroflavonol) phytoalexins from the papilionate legume Shuteria vestita.

Diffusates from the fungus-inoculated leaflets of Shuteria vestita have yielded four novel 3-hydroxyflavanone (dihydroflavonol) phytoalexins. From spectroscopic and chemical evidence, three of these phytoalexins have been identified as (2R,3R,2''R)--3,5,4'-trihydroxy-2'-isopropenyldihydrofurano (4'',5''; 6,7) flavanone (shuterol,1), (2R,3R)--3,5,7,4'-tetrahydroxy-6-(3,3-dimethylally) flavanone (shuterin, 2), and (2R,3R,2''R)--3,5,2',4'-tetrahydroxy-2''-isopropenyldihydrofurano (4'',5''; 6,7)flavanone (shuterone A, 3). The fourth compound (shuterone B, 4) is considered to be the 2S,3R stereoisomer of shuterone A.

Alcohol and hypertension: implications from research for clinical practice.

Despite the fact that recent epidemiological and laboratory studies appear to confirm that alcohol has an effect upon blood pressure, its impact has largely been ignored in clinical practice. This study was undertaken in an effort to answer four basic questions Is there an association between blood pressure and ethanol ingestion and if so is it causal or related to common genetic and/or environmental factors?; If an association exists, what is its likely physiological mechanism?; What additional studies are needed in order to further elucidate the relationship between alcohol and blood pressure?; What clinical recommendations, if any, are justified with our present state of knowledge?

Analysis of soybean sapogenins by high-performance liquid chromatography.

A method for the analysis of soybean sapogenins is described. The method is based on the extraction of soybean saponins from a defatted sample. The triterpene glycosides are then hydrolysed with subsequent analysis of the liberated sapogenins by high-performance liquid chromatography using gradient elution and mass detection. By use of a sapogenin/carbohydrate ratio, an estimate of the total saponin content can be made.

Plasma epinephrine concentration in healthy men: correlation with systolic pressure and rate-pressure product.

Relations among plasma epinephrine, norepinephrine and renin activity and systolic pressure, diastolic pressure, heart rate and the product of heart rate and systolic pressure (rate-pressure product) were evaluated in 31 healthy men whose arterial pressure spanned the range from normal to mildly elevated. Measurements were made during 60 minutes with the patient in the supine position and during 10 minutes of quiet standing. In the supine position, highly significant regressions were found between systolic pressure or rate-pressure product and plasma epinephrine, but not between these variables and norepinephrine or renin activity. A weakly significant correlation was also found between heart rate and norepinephrine. On standing, norepinephrine and epinephrine increased significantly. In this position, rate-pressure product was significantly related by regression analysis only with plasma epinephrine. Weakly significant correlations between systolic pressure and epinephrine and between heart rate and norepinephrine and epinephrine were also found. Plasma renin activity was not significantly correlated with arterial pressure, heart rate or rate-pressure product in either position. These results suggest that plasma epinephrine is a determinant of systolic pressure when postural reflexes are minimized and that epinephrine may participate in control of cardiac work load, as reflected by rate-pressure product in the absence of exercise or definable stress.

Effect of guanabenz on blood pressure responses to posture and exercise.

A single dose of guanabenz was examined for effects upon blood pressure, heart rate, plasma catecholamines, and plasma renin activity in a randomized, double-blind, crossover design. Eight patients were studied when supine, standing, and during submaximal exercise. Guanabenz reduced blood pressure in subjects who were supine or standing. Heart rate was lowered only in the supine subjects. Guanabenz induced reduction in plasma catecholamines subjects in all positions and the reduction correlated with the placebo level for both norepinephrine and epinephrine. Plasma renin activity was not significantly affected by guanabenz. The results indicate that the central alpha-agonist action of guanabenz reduces sympathoadrenal function to a greater extent in hyperadrenergic hypertensive patients than in those without this disorder.

Addition of acebutolol to diuretics in hypertension.

The effect of acebutolol as an antihypertensive beta receptor-blocking drug was evaluated in 15 patients that remained hypertensive while on diuretics. Observations were made in a small randomized double-blind trial in which the drug was compared to placebo and subsequently during a single-blind phase when the drug was given to those who had not responded to placebo. The dose range for acebutolol was 200 to 600 mg twice daily. Pretreatment plasma renin activity (PRA) and the response to intravenous saralasin infusion were assessed as predictors of the antihypertensive effect of acebutolol. None of six patients receiving placebo had a response of goal blood pressure or below; six of nine receiving acebutolol did respond (P less than 0.01). Acebutolol treatment induced reduction in diastolic pressure, heart rate, and PRA pooled from both phases of the study. There were no significant correlations between acebutolol therapy. Our data indicate that acebutolol is effective in diuretic-resistant hypertensive patients and that indices of the renin-angiotensin system are not predictors of the therapeutic response.

Plasma catecholamines in hypertension and pheochromocytoma determined using ion-pair reversed-phase chromatography with amperometric detection: investigation of the separation mechanism and clinical methodology.

The retention behavior of catecholamines (CAs) in ion-pair reversed-phase chromatography is examined. From the effects of pH, ionic strength and a secondary ion-pairing reagent (citric acid), under our chromatographic conditions, the retention behavior can be explained by assuming a mixed ion-exchange mechanism with octyl sulfate and citrate, on the column and in the mobile phase, respectively. The developed separation method was applied to the analysis of CAs in plasma samples purified by alumina adsorption and detected amperometrically. This method provides the basis for the determination of the short-term magnitude of CA response to physical and physiological interventions, as well as the baseline CA levels in essential hypertension and pheochromocytoma. The results seen for norepinephrine and epinephrine are consistent with eh funcitonal roles of these CAs as hormones or peripheral transmitters.

Quantitative determination of 3-methoxy-4-hydroxyphenylethyleneglycol and its sulfate conjugate in human lumbar cerebrospinal fluid using liquid chromatography with amperometric detection.

A sensitive and direct reversed-phase liquid chromatographic method with amperometric detection was developed for the determination of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). The concentrations of the free and sulfate conjugate of MHPG were measured in human lumbar cerebrospinal fluid. All samples were preconcentrated by extraction with ethyl acetate. Deconjugation of the sulfate form of MHPG was achieved by enzymatic hydrolysis with sulfatase. Peaks were identified on the basis of chromatographic behavior, ratio of responses at several oxidation potentials and the stopped-flow UV spectra of the collected fractions. The free MHPG content of 20 cerebrospinal fluid samples ranged between 0.720 and 19.51 ng/ml with the mean of 5.126 +/- 4.652 (S.D.) ng/ml. The sulfate conjugate of MHPG in 12 samples of cerebrospinal fluid ranged between 0.08 and 0.850 ng/ml with the mean value of 0.2365 +/- 0.2269 (S.D.) ng/ml. Although our results correlate well with the literature values, no attempt was made to interpret the quantitative data since samples were obtained from routine, diagnostic testing of patients admitted to the medical or neurologic services at the Mount Sinai Hospital.

Structural functions of the sweet pharmacophore.

The relative sweetness, onset times, and durations of response of D-glucose, D-xylose, D-quinovose, D-galactose, L-arabinose, and D-fucose were determined at four temperatures. The results can be interpreted by simple concepts of intramolecular hydrogen bonding which indicate that the so-called gamma-function of the tripartite AH,B, gamma sweet pharmacophore plays little or no part in sugar sweetness. Probably the Lemieux effect (intramolecular hydrogen bonding between the hydroxymethyl substituent and the 4-hydroxy group) is of overriding importance in determining sugar sweetness, and the separate features of intensity and time of response indicate distinct functions of chemoreception. The absence of a gamma-function in simple hydrophilic molecules such as glucose has already been emphasized. This function distinguishes them from the artificial sweetners such as saccharin, which may be 500 times or more sweeter than sucrose, depending on their stereostructure and lipophilicity.

Analysis of urinary metanephrines by reversed-phase high-performance liquid chromatography and electrochemical detection.

A sensitive and specific direct analysis of urinary normetanephrine (NMN) and metanephrine (MN) was achieved utilizing reversed-phase high performance liquid chromatography and electrochemical detection. Individual specimens from "control" subjects and those with pheochromocytoma were hydrolyzed and the metanephrines separated from other urinary constituents by elution with ammonia from a Dowex CG-50 resin. Chromatographic peaks were identified by retention behavior, co-chromatography with reference compounds, ratio of responses at various oxidation potentials and stopped-flow UV spectra of the collected fractions. The NMN and MN content for the control subjects was between 0.086 and 0.21 (mean - 0.14) microgram/mg creatinine and 0.012 and 0.092 (mean = 0.039) microgram/mg creatinine, respectively. The values for subjects with pheochromocytoma varied from 1.5 to 27.5 (mean = 9.9) microgram/mg creatinine for NMN and 0.10 to 1.60 (mean = 0.86) microgram/mg creatine for MN. The patient with ganglioneuroma had an NMN of 4.1 and an MN of 0.80 microgram/mg creatinine. While this method permits discrimination between those patients with pheochromocytoma and the overwhelming majority of hypertensive patients, it may ultimately be further extended to separate normal subjects from those with more subtle derangements in catecholamine metabolism.

Metabolism of D, L-3H-norepinephrine in essential hypertension.

Defective control of the cardiovascular system by the sympathetic nerves continues to be incriminated as the potential primary physiologic defect in essential hypertension (EH). The need to measure sympathetic tone has progressed from physiologic mensuration by assessment of reflex and pharmacological responses to the recent assay of norepinephrine (NE) and its congeners in both urine and plasma. The way in which the body handles D,L-B-3H-NE represents yet another technique by which to evaluate sympathetic function. Previous studies of EH by this method demonstrated more rapid plasma disappearance of 3H-NE as well as elevated 24 hour tritium accumulation in the urine following D,L-B-3H-NE injection. The present study of 7 normotensive subjects and 7 patients with EH was designed to depict more precisely these abnormalities in 3H-NE-metabolism. Following a one minute injection of 8 micrograms D,L-B-3H-NE, (200 microCi) intravenously, the excretion of unlabeled endogenous metabolites and their labeled congeners was assayed. By these means one could estimate catecholamine synthesis, turnover of the labeled pools, and by comparison of relative specific activities of the metabolites, gain some insight into the distribution of the injected material. Alternative catabolic pathways were evaluated by measurement of the excretion of 3H2O. Patients with EH excreted more label per 24 hours, revealed a more rapid decline of 3H2O excretion and lower specific activity of normetanephrine (NM). These findings are compatible with changes in pool dynamics and distribution of administered label which gave additional support to the concept of adrenergic dysfunction in association with essential hypertension.

Urinary tritium excretion following intravenous 3H-norepinephrine administration in hypertensive rats.

Spontaneously hypertensive rats (SHR), salt-resistant (SRR), salt-sensitive (SSR), and Sprague-Dawley DOC-salt nephrectomized rats were tested by evaluation of tritiated norepinephrine uptake and blood pressure with diets containing various amounts of sodium. Only Sprague-Dawley rats who had been both nephrectomized and given DOC on a high salt diet (8%) illustrated the elevated tritium excretion similar to that observed in human subjects with essential hypertension.