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P-440 Key Words: Left Ventricular Hypertrophy, Central Pressure, Augmentation Index

Microvascular function in human essential hypertension Angela Shore;John Tooke; Journal of Hypertension

Fifteen unselected patients who had essential hypertension and whose average supine blood pressure when they were not receiving any treatment and their usual sodium intake was 162/107 mm Hg were treated with captopril 50 mg twice daily. After one month's treatment their supine blood pressure had decreased to 149/94 mm Hg. They were then instructed to reduce their sodium intake to about 80 mmol(mEq)/day. After two weeks of moderate sodium restriction they were entered into a double blind randomised crossover study comparing the effect of 10 Slow Sodium tablets (100 mmol sodium chloride) with matching placebo tablets while continuing to take captopril and restrict sodium in their diet. After one month of taking placebo their mean supine blood pressure was 137/88 mm Hg with a urinary sodium excretion of 83 mmol/24 h, while after one month of taking Slow Sodium tablets their mean supine blood pressure was 150/97 mm Hg (p less than 0.001) with a sodium excretion of 183 mmol/24 h. The mean supine blood pressure during moderate sodium restriction therefore decreased by 9% and correlated significantly with the reduction in urinary sodium excretion. These results suggest that the combination of treatment with a moderate but practical reduction in sodium intake and an angiotensin converting enzyme inhibitor is effective in decreasing the blood pressure in patients with essential hypertension. This combined approach overcomes some of the objections that have been made to salt restriction alone and to converting enzyme inhibitors alone.

The effect of plasma from normotensive and hypertensive subjects on the binding of [3H]ouabain on human erythrocytes was investigated. The binding of [3H]ouabain on human erythrocytes was saturable and highly specific; linear Scatchard plots indicated the presence of a single type of binding site. Human plasma decreased the binding of [3H]ouabain on its receptor to a greater extent than could be accounted for by the plasma potassium concentration. The level of this circulating ouabainlike factor (or factors) was quantitated using a radioreceptor assay. Plasma from 22 hypertensive subjects (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg) displayed higher levels than that from 24 normotensive subjects; furthermore there was a positive and significant correlation (r = 0.42, n = 46, p less than 0.004) between the ouabainlike content and the individual subject's systolic blood pressure. The receptor assay described is relatively simple and should be useful for further work on the nature and clinical importance of the endogenous ouabainlike factor.

Plasma levels of immunoreactive atrial natriuretic peptides (IrANP) have been measured in 8 normotensive subjects during alterations in dietary sodium intake. Subjects were studied on their normal sodium intake (2 days) then on a low sodium intake (7 days, 10 mmols Na+/day) and subsequently on a high sodium intake (14 days, 350 mmols Na+/day with the diets being given in a fixed order. Plasma levels (mean +/- S.E.M.) of IrANP on a normal sodium diet were 7.3 +/- 0.9 pg/ml; 4.5 +/- 0.8 on the 7th day of a low sodium intake and 10.8 +/- 1.3; 16.6 +/- 3.3; 15.5 +/- 4.2; 15.6 +/- 2.3 pg/ml respectively or the 1st, 3rd, 10th and 14th day on the high sodium intake. Changes in plasma IrANP were closely associated with changes in urinary sodium excretion. These results suggest that in normal subjects the atrial natriuretic peptides may play an important role in the adaptation to increases in dietary sodium intake both on a short and on a longer term basis.

1. Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in eight normal healthy volunteers before and during mineralocorticoid escape. 2. Mean plasma ANP on a fixed sodium intake before fludrocortisone was 6.5± sem 1.1 pg/ml. Within 24 h of fludrocortisone administration there was a significant increase in plasma ANP which continued to increase daily reaching a plateau by day 4 (14.9 ± 2.4 pg/ml) to day 7 (15.1 ± 2.6 pg/ml). 3. The rise in plasma ANP was closely related to the amount of sodium retained during the fludrocortisone treatment and the sodium ‘escape’ occurred by days 4 to 7. 4. These results support the concept that ANP could play an important hormonal role in overcoming the sodium-retaining effects of mineralocorticoids in man.

The effects of the addition of a calcium entry antagonist, nifedipine (20-mg tablet twice a day), to an angiotensin converting enzyme inhibitor, captopril (25 mg three times a day), and the addition of captopril to nifedipine were observed in two separate studies in patients with essential hypertension. After 4 weeks of captopril therapy alone, mean arterial pressure fell by 12 mm Hg, and with the addition of nifedipine to captopril for a further month, blood pressure fell by an additional 10 mm Hg. In a separate group of patients treated with the same doses, mean arterial pressure fell by 17 mm Hg with nifedipine treatment alone; when captopril was added to the nifedipine therapy for an additional month, mean arterial pressure fell by a further 11 mm Hg. These blood pressures were measured 2 hours after the last dose; however, there was less of a fall in blood pressure when it was measured 12 hours after the last dose. This study confirms that captopril and nifedipine have a marked additive effect on blood pressure in whichever order they are given, but it shows that the combination is relatively short-acting.

1. Plasma immunoreactive atrial natriuretic peptide (ANP) and urinary sodium excretion were measured in six normal male subjects before, during and for 195 min after a 60 min infusion of 2 litres of saline (0.9% NaCl, 308 mmol of Na+). 2. During the saline infusion, there was a significant increase in plasma ANP and urinary sodium excretion and a significant decrease in plasma renin activity, aldosterone, albumin, creatinine and packed cell volume. 3. The maximal rise in mean plasma ANP occurred 15 min after stopping the infusion and the maximal rise in mean urinary sodium excretion in the collection period 30 min later. 4. Plasma ANP then decreased so that by the end of the study the level was the same as before the saline infusion. However, at this time, 195 min after the saline infusion was stopped, there was still a net positive sodium balance of 220 mmol and urinary sodium excretion remained significantly elevated. 5. Our results are compatible with the concept that increased ANP secretion may play a role in the immediate increase in sodium excretion after a saline load. However, they also suggest that other mechanisms may be more important for the longer term increase in sodium excretion.

Endothelial dysfunction and inflammation in asymptomatic proteinuria.BackgroundProteinuria is associated with vascular risk and a systemic increase in vascular permeability. Endothelial dysfunction occurs early in atherosclerosis and modulates vascular permeability. Vascular risk and chronic inflammation are associated. This study investigates whether the increased vascular permeability in proteinuria reflects systemic endothelial dysfunction and chronic inflammation.MethodsTwenty-one patients with asymptomatic proteinuria (1.29 g/24 h; range 0.18 to 3.17) and 21 matched controls were studied. Microvascular endothelial function was assessed using acetylcholine iontophoresis. Maximum microvascular hyperemia (MMH) was assessed by flux response to local skin heating. Macrovascular endothelial function was assessed by flow-associated dilation (FAD) in the brachial artery using ultrasound. von Willebrand factor (vWF) was measured as a marker of endothelial activation. Low-grade inflammation was assessed by measurement of circulating C-reactive protein (CRP) values using a high sensitivity assay.ResultsFAD was impaired in proteinuric subjects (AP) compared to controls [1.8 (0.2 to 5.3) AP vs. 3.8 (1.5 to 6.2) C %; P = 0.014]. There was no significant difference between groups in MMH or in the response to acetylcholine iontophoresis. The AP group had a higher CRP [4.0 (0.5 to 39.0) AP vs. 0.2 (0.1 to 21.3) C mg/L; P < 0.001] and tendency to higher vWF [101.5 (67.0 to 197.0) AP vs. 77.5 (45.0 to 185.0) C IU/dL; P = 0.046] compared to controls. In the AP, but not control, group there was an inverse correlation between CRP and microvascular function as determined by acetylcholine iontophoresis (r = -0.509; P = 0.018).ConclusionsIn AP subjects there is evidence of macrovascular endothelial dysfunction remote from the kidney and of low-grade inflammation that is associated with microvascular endothelial dysfunction.

Six patients with essential hypertension underwent a randomized cross over design study to investigate the effect of supplementing a 10 mmol/day sodium diet for a period of 5 days with either 120 mmol sodium chloride (Slow Sodium, Ciba, Horsham, UK) or 122 mmol sodium in the presence of other anions, mainly phosphate (Phosphate, Sandoz, Feltham, UK). With both sodium salts, urinary sodium excretion was increased. The calculated amount of sodium retained was similar for both the sodium chloride and sodium phosphate periods. However, with the addition of sodium chloride to the low-salt diet, there were increases in supine mean blood pressure whereas with the addition of sodium phosphate no change in mean blood pressure occurred. The supine mean blood pressure after supplementation with sodium chloride (119.8 +/- 4.3 mmHg) was significantly greater than that after sodium phosphate (113.3 +/- 4.5 mmHg), similarly, the standing mean blood pressure was greater after addition of sodium chloride than of sodium phosphate (122.3 +/- 4.20 versus 115.4 +/- 3.0 mmHg). With both salts there were similar but non-significant increases in weight and reductions in plasma renin activity (PRA) and plasma aldosterone (PA).

The control of blood pressure in 44 patients on continuous ambulatory peritoneal dialysis (CAPD) for 7 ± 4 months was studied in relation to measurements of exchangeable sodium (NaE), plasma renin activity (PRA) and plasma aldosterone concentration (PA). Comparisons were made with 21 patients on hemodialysis (HD) for 50 ± 13 months and with 32 normal subjects.

Plasma renin activity (PRA), plasma renin concentration (PRC), plasma angiotensin II concentration (AII), plasma and urinary aldosterone (PA, UA) and urinary sodium excretion (UNaV) were measured in 51 normal controls, 16 patients with decompensated cirrhosis (i.e. ascites and/or oedema present) in sodium equilibrium (Group 1) and 13 patients with decompensated cirrhosis in a phase of active sodium retention (Group 2). In Group 1 the mean supine and erect values, although lower, were not significantly different from controls. In Group 2 the mean values were significantly elevated, but several individual values were within the normal range; there were significant direct relationships between plasma renin activity and plasma renin concentration (r = 0.85, p less than 0.001 erect), plasma renin concentration and plasma angiotensin II concentration (r = 0.86, p less than 0.001 erect), and plasma angiotensin II concentration and plasma aldosterone (r = 0.70, p less than 0.01 erect). In Group 2 there was an inverse correlation between urinary sodium excretion and both urinary aldosterone (r = -0.50) and erect plasma aldosterone (r = -0.36) but, perhaps because of the narrow range of sodium excretion rates, significance was not reached. The normal values in Group 1 indicate that hyperaldosteronism is not essential for the maintenance of established ascites, but do not exclude a role for aldosterone in the control of sodium excretion if it is accepted that renal tubular sensitivity to aldosterone is increased in these patients. In Group 2, the raised mean plasma and urinary aldosterone levels and the trend towards an inverse relationship with urinary sodium excretion suggests a role for aldosterone in the active retention of sodium. It appears that stimulation of the renin-angiotensin system is the major factor in the elevation of plasma aldosterone; there was no relationship between plasma aldosterone and either plasma sodium or potassium levels. The mechanism of renin hypersecretion is unclear but this may represent part of a sympathetically mediated response in order to maintain blood pressure. The close relationship between plasma renin activity and plasma renin concentration indicates that the former is a valid measure of circulating renin levels in cirrhosis, despite low renin-substrate levels.

Abnormalities of calcium binding and calcium transport in cells from hypertensive subjects or animals have been previously described. Total cell sodium is reported to be increased in white blood cells from hypertensive subjects; thus by analogy with Blaustein's proposal for the vascular smooth muscle cell, mononuclear leucocyte cytosolic calcium might be increased via a reduction of the Na-Ca exchange. Using the fluorescent calcium indicator, quin 2, cytosolic calcium was measured in mononuclear leucocytes from 22 hypertensive and 19 normotensive subjects. There was no significant difference between the mononuclear leucocyte cytosolic calcium level in the two groups. Incubation of the cells with 10(-4) M ouabain reduced 86 rubidium (86Rb) uptake by 80% of the control value but failed to alter cytosolic calcium. These findings are consistent with a minimal role of the Na-Ca exchange in the mononuclear leucocyte and may explain why the cytosolic calcium was not increased in hypertension despite the previous reports of increased total cell sodium in white blood cells.

Plasma levels of atrial natriuretic peptide (ANP) in 106 patients with essential hypertension with a supine mean blood pressure (mean +/- SEM) of 128.9 +/- 1.6 mmHg and not on treatment were significantly higher than those in 47 normotensive subjects (supine mean blood pressure 93.9 +/- 1.2 mmHg) with mean values of 17.2 +/- 1.1 and 8.6 +/- 0.6 pg/ml, respectively (P less than 0.001). Similar results were found in a subgroup of 35 hypertensive patients identically matched in terms of age, sex, and race with 35 normotensive subjects. Plasma levels of ANP were correlated significantly with age in normotensive subjects and with age and blood pressure in the hypertensive patients. In 12 hypertensive patients studied on a low (10 mmol sodium/day), on their usual sodium intake (around 120 mmol sodium/24 hr) and on a high (350 mmol sodium/day) intake, plasma ANP increased approximately twofold by the fifth day of the high sodium intake, but there was no significant difference between the plasma levels on their usual sodium intake and those on the fifth day of the low sodium intake. Supine mean blood pressure on the patients' usual sodium intake was 119.3 +/- 2.7 mmHg and was reduced to 110.0 +/- 3 mmHg by the fifth day of the low sodium intake (P less than 0.005). However, there was no significant difference between the blood pressure levels on their usual and high sodium intake (118.3 +/- 3.0 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Exchangeable sodium, plasma renin activity, plasma angiotensin II and plasma aldosterone were measured in forty-six control subjects, nineteen patients with chronic non-cirrhotic liver disease and twenty patients with compensated cirrhosis (i.e. without ascites or oedema). In the three groups respectively, mean exchangeable sodium (mmol/kg lean body mass) was 53 (SD = 3), 50 (SD = 5) and 52 (SD = 8). Mean plasma renin activity (pmol l(-1) min(-1)) was 3.2, 3.1 and 3.0 supine and 6.2, 6.2 and 5.1 erect. Mean plasma angiotensin II (pmol l(-1) was 7.3, 5.8 and 6.6 supine and 10.6, 7.9 and 9.0 erect. Mean plasma aldosterone (pmol l(-1)) was 82, 64 and 77 supine and 188, 133 and 121 erect. There were no significant differences among the mean values of any of these variables. These findings indicate that, on the basis of exchangeable sodium measurements, sodium retention is not present in compensated liver disease and that the renin--angiotensin--aldosterone system is essentially normal.

1. Eight normotensive subjects were studied in a randomized crossover trial of a high calcium diet (1800 mg of calcium/day) for a week against a low calcium diet (200 mg of calcium/day) for a further week. 2. The subjects were placed on a diet containing 200 mg of calcium/day throughout the study and the high calcium diet was achieved by supplementing the low calcium diet with calcium glubionate and galactogluconate. Sodium and potassium intake were kept constant throughout the study. 3. Twenty-four hour urinary sodium, potassium, calcium and phosphate were measured daily. 4. In spite of a highly significant increase in calcium excretion from the low to the high calcium diet (P < 0.0001), there was no increase in sodium or change in potassium excretion with the increased calcium intake. A transient but significant fall in urinary sodium excretion was observed up to the fourth day of the high calcium diet (P = 0.021). Twenty-four hour urinary phosphate excretion fell significantly on the high calcium diet (P < 0.0001). Body weight, blood pressure, plasma renin activity, aldosterone, plasma creatinine and serum ionized calcium did not change. 5. These results suggest that a short-term increase in calcium intake in normotensive subjects does not increase urinary sodium and potassium excretion.

Eighteen unselected patients with untreated mild to moderate essential hypertension, whose average supine blood pressure after 2 months' observation on no treatment was 154/103 mmHg, were entered into a double-blind randomized crossover study of 1 month's treatment with calcium lactate gluconate (40 mmol of elemental calcium/day) and treatment with placebo for a further month. Despite a significant increase in total plasma calcium (P less than 0.01) and in 24-h urinary excretion of calcium (P less than 0.025) while taking calcium lactate gluconate, there was no fall in blood pressure with calcium supplementation compared to treatment with placebo.

The glomerular basement membrane (GBM) is an important component of the filtration barrier that is the glomerular capillary wall. Previously GBM permeability has been investigated only under static pressures and often within a supraphysiological range. We used Matrigel as a model of GBM and formed membranes at the base of a filtration chamber. We measured membrane permeability under static and dynamic pressures. Matrigel membranes were size and charge selective toward neutrally and negatively charged dextrans. Their permeability (as measured by hydraulic conductivity) was found to decrease from 1.61 ± 0.06 to 0.75 ± 0.07 × 10−6cm ⋅ s−1⋅ cmH2O−1as static pressure increased from 6 to 78 cmH2O, an effect attributed to membrane compression. In comparison to static pressure, sinusoidal pressure waves with a mean pressure of 50 cmH2O decreased membrane permeability, e.g., fluid flux was reduced by a maximum of 2% to a value of 5.47 ± 0.38 × 10−5cm/s; albumin clearance was reduced by a maximum of 5.2% to a value of 9.63 ± 1.06 × 10−6ml ⋅ cm−2⋅ s−1. Such changes were affected by the frequency of pressure wave application and could be attributed to a switching on and off of the membrane compression effect.

The influence of gender, local temperature, and systemic blood pressure on human capillary pressure is unknown. Finger nail fold capillary pressure was therefore directly measured in 74 healthy supine volunteers (40 female) at midaxillary level. Capillary pressure was lower in women than in men (15.9 +/- 3.0 vs. 18.2 +/- 2.3 mmHg; P = 0.001), particularly in premenopausal women, but was not related to systolic, diastolic, or mean blood pressure. Capillary pulse pressure amplitude was related to skin temperature, an effect more marked in women (P = 0.003). There was a significant association between skin temperature and the time taken for the systolic pressure rise to reach the capillary, in women only (r = -0.69, P < 0.001). Increasing age reduced the high-frequency waves in the pressure waveform [2nd harmonic percentage of fundamental: r = -0.52 and P = 0.002 (women), r = -0.52 and P = 0.004 (men)]. Thus mean capillary pressure and the pressure waveform may be influenced by gender, age, and skin temperature, illustrating the necessity to adequately match control groups during assessments of capillary pressure pathophysiology.

The volume, velocity, and acceleration of ascending aortic blood were measured in man using a pulsed Doppler ultrasound instrument, with online spectral analysis and offline computer processing of velocity data. This system was firstly validated in a test rig capable of generating pulsatile flow of talc particles in water at physiological velocities and accelerations in a model aorta. Doppler measurements correlated well (r≥0.90) with simultaneous electromagnetic measurements of stroke volume, peak ejection velocity, and maximum acceleration in this rig. In vivo validation was performed firstly by comparing simultaneous Doppler and thermodilution cardiac output (![Graphic][1] ) measurements; this yielded the following regression equation: Doppler ![Graphic][2] = 0.90 × thermodilution ![Graphic][3] + 0.03 litre·min−1, r=0.92; n=38. Beat by beat measurements were then validated against simultaneous invasive aortic blood velocity measurements made using a Mills electromagnetic cathetertip probe. When paced single beats of different size were compared within subjects the correlation coefficients between Doppler and electromagnetic measurements averaged 0.89 for stroke volume, 0.91 for peak ejection velocity, and 0.79 for maximum acceleration in five subjects. The absolute values for velocity and acceleration from the Doppler system differed significantly from the absolute values given by the electromagnetic system and this difference was not consistent between subjects. It is concluded that the Doppler system can non-invasively record relative changes in left ventricular ejection in man. [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif

OBJECTIVE—Low birth weight has been linked to an increased risk of type 2 diabetes and cardiovascular disease in adult life. The fetal insulin hypothesis proposed that a genetic predisposition to insulin resistance may also influence vascular development. Therefore, impaired vascular function may be an intrinsic abnormality in low–birth weight infants that antedates clinical features of the insulin resistance syndrome. RESEARCH DESIGN AND METHODS—Two groups of 3-month-old term infants were included in the study: 17 infants of lowest quartile birth weight (LQBW) and 21 infants of highest quartile birth weight (HQBW). Three aspects of skin microvascular function were examined; response to local heating, response to acetylcholine iontophoresis, and capillary density. RESULTS—Median (interquartile ranges) birth weights of the LQBW and HQBW infants were 3,140 g (2,738–3,254) and 3,920 g (3,750–4,020), respectively. Skin maximal hyperemic response to local heating was 2.14 V (1.68–2.30) in the LQBW group vs. 2.44 V (1.96–2.90) in the HQBW group (P = 0.020), and the endothelium-dependent vasodilatory response was 1.03 V (0.62–1.32) in the LQBW group vs. 0.78 V (0.45–1.32) in the HQBW group (P = 0.297). Capillary density in the LQBW and HQBW groups were 46.3 mm−2 (40.1–53.7) and 44.1 mm−2 (41.7–56.0), respectively (P = 0.736). CONCLUSIONS—Skin maximal hyperemic response was lower in LQBW infants, although no reduction in capillary density or defect in endothelium-dependent vasodilatation was observed. Such a lower maximal hyperemic response in early life in LQBW subjects who are at risk for type 2 diabetes and cardiovascular disease supports the hypothesis that impaired microvascular function is an early antecedent to diabetes in later life.

Seventeen unselected patients with mild to moderate essential hypertension and whose average supine blood pressure after two months' observation with no treatment was 154/100 mm Hg were entered into a double blind randomised crossover study of one month's treatment with magnesium aspartate (15 mmol magnesium/day) and treatment with placebo for a further month. This preparation of magnesium was well tolerated and did not cause diarrhoea. Despite a significant increase in plasma magnesium concentration and a significant increase in urinary excretion of magnesium while taking magnesium aspartate there was no fall in blood pressure compared with either treatment with placebo or values before treatment. The results provide no evidence for a role of dietary magnesium in the regulation of high blood pressure and are contrary to recent speculations.

1. The effects of synthetic human and rat atrial peptides on sodium and potassium ion transport has been investigated in intact human erythrocytes. 2. The effects of these peptides have been tested on the active, sodium pump-dependent (ouabain-sensitive) and on the sodium-potassium cotransport system (bumetanide-sensitive) with 86Rb used as a tracer. 3. Human (α-ANP, 28 amino acids) or rat (atriopeptin III) atrial peptides, over a wide range of concentrations, did not influence the uptake of 86Rb in either the ouabain-sensitive or the bumetanide-sensitive transport system. 4. These results suggest that the natriuretic effect of the atrial peptides is not mediated through inhibition of the sodium pump or the loop-diuretic-sensitive Na-K cotransport.

1. In order to investigate the effects of K+ depletion on renal function, micropuncture studies were performed on anaesthetized rats which had been kept on a K+-deficient diet for 2 weeks; results were compared with those from control animals. 2. In the K+-depleted animals, values for total glomerular filtration rate and single-nephron filtration rate were significantly lower than in controls. Urine osmolality was also reduced; this was associated with reductions in the osmolality, Na+ concentration and K+ concentration of papillary interstitial fluid. No significant difference between urine and papillary osmolality was observed. 3. Fractional reabsorption by the proximal convoluted tubule was enhanced in the K+-depleted animals; end-proximal fluid delivery was markedly reduced. 4. Absolute, but not fractional, delivery of K+ to the beginning of the distal tubule was reduced in the K+-depleted animals. In contrast to observations in control rats, no net secretion of K+ into the distal tubule occurred and there was indirect evidence of K+ reabsorption in the collecting duct. 5. K+ depletion was associated with reductions in the delivery of Na+ and water to early and late regions of the distal tubule, whereas excretion rates of Na+ and water were unaffected. 6. It is suggested that the reduction in Na+ delivery to the loop of Henle (arising from the changes in filtration rate and proximal tubular reabsorption) might contribute to the reduced medullary osmotic concentration observed during K+ depletion. Reductions in fractional reabsorption of Na+ and water in the collecting duct might result from lowered plasma aldosterone levels and the reduced medullary osmolality.

The introduction of the servonulling technique by Wiederhielm in 1963 allowed for the first time continuous and dynamic recording of capillary blood pressure (CP). In 1979 Mahler used this technique for the first measurements in humans. Data analysis was limited to manual analysis of chart recordings. Nowadays fast analog-digital converters with ay high sampling frequency are used for data recordings, and consequently there is a need for an easy-to-use software for data analysis of CP data. The presented newly developed computer software allows analysis of mean CP, taking into account the zero pressure measured before and after capillary cannulation. The simultaneously recorded electrocardiogram R wave is used as a marker for the calculation of the mean capillary pulse pressure waves and of their characteristic data. This may help determine the significance of the capillary pulse waveform for microvascular function. Changes in the pulse waveform may be the only detectable difference between patients and healthy controls. Analysis of simultaneously recorded temperature, the display of markers for valid readings, and the possibility of excluding nonvalid data or artefacts from analysis are additional features.

Measurement of the renal vein renin ratio (RVRR) is commonly used to predict the response of blood pressure to surgery in hypertensive patients with unilateral renovascular disease. We have reviewed our experience in 37 such patients in whom renal vein renin levels were measured basally and after stimulation of renin secretion with intravenous diazoxide or tilting. Twenty-four patients were cured or improved. When a basal ratio of greater than or equal to 1.5 (diseased: normal kidney) was taken as a positive test the false positive rate was 39% and the false negative rate 71%, there being little difference in outcome between those with ratios above or below 1.5. No other threshold value of RVRR identified those responding to surgery, and acute stimulation of renin secretion did not increase the value of the test. We conclude that the RVRR is of no prognostic value in the surgical treatment of hypertension due to unilateral renovascular disease.

The importance of the dynamic nature of perfusion pressure within the peripheral microcirculation is increasingly recognised. Capillary pressure is determined not only by arterial inflow pressure, but is also subject to a variety of local and systemic influences which have been shown to affect both mean pressure and the capillary pulse waveform. To what extent changes in central pulse waveform influence capillary pressure has yet to be determined. By using a dynamic technique of capillary pressure measurement in human subjects with aortic stenosis, we have been able to show that the characteristics of the pulse waveform typically associated with large vessels in this condition are also readily detectable at a capillary level despite local influences. However, changes in the rate of pulse wave transmission described in large arteries were not apparent at a microvascular level. Unlike mean capillary pressure and capillary pulse pressure, pulse waveform in the capillary mimics central haemodynamics.

Barrett's oesophagus (BE) is a premalignant condition that can progress to oesophageal adenocarcinoma. Endoscopic surveillance aims to identify potential progression at an early, treatable stage, but generates large numbers of tissue biopsies. Fourier transform infrared (FTIR) mapping was used to develop an automated histology tool for detection of BE and Barrett's neoplasia in tissue biopsies. 22 oesophageal tissue samples were collected from 19 patients. Contiguous frozen tissue sections were taken for pathology review and FTIR imaging. 45 mid-IR images were measured on an Agilent 620 FTIR microscope with an Agilent 670 spectrometer. Each image covering a 140 μm × 140 μm region was measured in 5 minutes, using a 1.1 μm2 pixel size and 64 scans per pixel. Principal component fed linear discriminant analysis was used to build classification models based on spectral differences, which were then tested using leave-one-sample-out cross validation. Key biochemical differences were identified by their spectral signatures: high glycogen content was seen in normal squamous (NSQ) tissue, high glycoprotein content was observed in glandular BE tissue, and high DNA content in dysplasia/adenocarcinoma samples. Classification of normal squamous samples versus ‘abnormal’ samples (any stage of Barrett's) was performed with 100% sensitivity and specificity. Neoplastic Barrett's (dysplasia or adenocarcinoma) was identified with 95.6% sensitivity and 86.4% specificity. Highly accurate pathology classification can be achieved with FTIR measurement of frozen tissue sections in a clinically applicable timeframe.

Etude chez 12 malades atteints d'hypertension essentielle non compliquee, sans traitement medicamenteux. Les taux plasmatiques du peptide sont modifies par les changements d'apport en sodium, comme pour les sujets normaux, mais uniquement lors de l'augmentation de l'ingestion de sodium. La restriction semble sans effet