Further evidence of a prolonged hypotensive and a bradycardic effect after mandibular extension in normal volunteers.

We previously reported that in normotensive humans submaximal mouth opening (mandibular extension) obtained by an ad hoc dilator (spring device), associated with partial masticatory movements and prolonged for 10 minutes is followed by a long-lasting reduction of blood pressure (BP) and heart rate (HR). Similar results were obtained by us in anesthetized rats. A recent independent study failed to confirm the results in the normotensive human. We reassessed, in 25 normotensive volunteers, the effects on BP and HR of mandibular extension obtained by the spring device associated with partial masticatory movements compared to a control procedure, consisting in keeping a tongue depressor between the incisor teeth. Both procedures were applied for 10 minutes and systolic BP (SBP), diastolic BP (DBP) and HR were measured every 10 minutes by an automatic recorder, for 30 minutes before and 120 minutes after the procedures in seated subjects watching nature documentary films on laptop screen.Baseline levels (mean of the last 3 measurements before procedure) did not significantly differ between the experimental and control sessions. Two way repeated measures ANOVA on absolute (recorded) values did not reveal a significant main effect of treatment for SBP, DBP and HR, but a significant main effect of time (P<0.001) for BP and HR. In addition, a significant interaction of time and treatment was found for SBP (P<0.001) and DBP (P=0.005), but not for HR. In addition, two way repeated measures ANOVA was done on changes from baseline obtaining a significant main effect of treatment (P<0.001) and time (P<0.001) and a significant interaction of time and treatment for SBP (P<0.001) and DBP (P<0.01). Post-hoc comparisons revealed significantly lower values for SBP and DBP in experimental compared to control values at almost all times and this decrement was by about 5 mmHg. Furthermore, for both absolute values and changes from baseline, the interaction effect was, for BP, of a qualitative type as indicated by an opposite effect in the time-course between control and experimental sessions. This study thus provides confirmatory evidence that submaximal mouth opening for a relatively brief time is followed by prolonged albeit small reductions of BP in normotensive human volunteers.

Persistent effects after trigeminal nerve proprioceptive stimulation by mandibular extension on rat blood pressure, heart rate and pial microcirculation.

The trigemino-cardiac reflex is a brainstem reflex known to lead to a decrement in heart rate and blood pressure, whereas few data have been collected about its effects on the cerebral hemodynamic. In this study we assess the in vivo effects of trigeminal nerve peripheral stimulation by mandibular extension on pial microcirculation and systemic arterial blood pressure in rats. Experiments were performed in male Wistar rats subjected to mandibular extension obtained inserting an ad hoc developed retractor between the dental arches. Mean arterial blood pressure and heart rate were recorded and the pial arterioles were visualized by fluorescence microscopy to measure the vessel diameters before (15 minutes) during (5-15 minutes) and after (80 minutes) mandibular extension. While in control rats (sham-operated rats) and in rats subjected to the dissection of the trigeminal peripheral branches mean arterial blood pressure, heart rate and pial microcirculation did not change during the whole observation period (110 minutes), in rats submitted to mandibular extension, mean arterial blood pressure, heart rate and arteriolar diameter significantly decreased during stimulation. Afterward mean arterial blood pressure remained reduced as well as heart rate, while arteriolar diameter significantly increased evidencing a vasodilatation persisting for the whole remaining observation time. Therefore, trigeminal nerve proprioceptive stimulation appears to trigger specific mechanisms regulating systemic arterial blood pressure and pial microcirculation.

The ovarian cycle as a factor of variability in the laboratory screening for primary aldosteronism in women.

Primary aldosteronism is increasingly investigated in hypertension being associated with an elevated cardiovascular risk. Aldosterone has been reported to increase in the luteal phase in normal women but to our knowledge the influence of the ovarian cycle on the first screening for primary aldosteronism (that is, on the levels of plasma aldosterone and its relationship to PRA levels) was never investigated. We measured hormonal levels during one cycle in 26 low-renin mild hypertensive outpatients. LH, FSH, 17 beta-estradiol, progesterone, aldosterone and PRA were assayed at the seventh, fourteenth, twenty-first and twenty-eighth days of the cycle after 30 min of recumbency. Aldosterone and PRA increased from the seventh (follicular phase) to twenty-first day (luteal phase) from 11.2 to 17.8 ng 100 ml(-1) and from 0.23 to 0.35 ng ml(-1) h(-1), respectively (both P=0.004) The proportion of patients with aldosterone >15 ng 100 ml(-1) significantly increased from the follicular to the luteal phase, (8/26 vs 19/25, P=0.018); a similar increase was found for Aldosterone-PRA Ratio >30 combined with either a minimum PRA value of 0.5 ng ml(-1) h(-1) or aldosterone >15 ng 100 ml(-1) (7/26 vs 16/25 and 7/26 vs 17/25 respectively, P<0.05). Aldosterone was positively related to PRA and progesterone. Higher aldosterone levels may be frequently encountered in the second part of the ovarian cycle in low-renin hypertensive women. This variability appears to be an important factor to be taken into account in the first-step laboratory screening for primary aldosteronism and should be considered in the process of standardization of the diagnostic work-up for this disease.

Insulin resistance and vasodilation in essential hypertension. Studies with adenosine.

Insulin-mediated vasodilation has been proposed as a determinant of in vivo insulin sensitivity. We tested whether sustained vasodilation with adenosine could overcome the muscle insulin resistance present in mildly overweight patients with essential hypertension. Using the forearm technique, we measured the response to a 40-min local intraarterial infusion of adenosine given under fasting conditions (n = 6) or superimposed on a euglycemic insulin clamp (n = 8). In the fasting state, adenosine-induced vasodilation (forearm blood flow from 2.6 +/- 0.6 to 6.0 +/- 1.2 ml min-1dl-1, P < 0.001) was associated with a 45% rise in muscle oxygen consumption (5.9 +/- 1.0 vs 8.6 +/- 1.7 mumol min-1dl-1, P < 0.05), and a doubling of forearm glucose uptake (0.47 +/- 0.15 to 1.01 +/- 0.28 mumol min-1dl-1, P < 0.05). The latter effect remained significant also when expressed as a ratio to concomitant oxygen balance (0.08 +/- 0.03 vs 0.13 +/- 0.04 mumol mumol-1, P < 0.05), whereas for all other metabolites (lactate, pyruvate, FFA, glycerol, citrate, and beta-hydroxybutyrate) this ratio remained unchanged. During euglycemic hyperinsulinemia, whole-body glucose disposal was stimulated (to 19 +/- 3 mumol min-1kg-1), but forearm blood flow did not increase significantly above baseline (2.9 +/- 0.2 vs 3.1 +/- 0.2 ml min-1dl-1, P = NS). Forearm oxygen balance increased (by 30%, P < 0.05) and forearm glucose uptake rose fourfold (from 0.5 to 2.3 mumol min-1dl-1, P < 0.05). Superimposing an adenosine infusion into one forearm resulted in a 100% increase in blood flow (from 2.9 +/- 0.2 to 6.1 +/- 0.9 ml min-1dl-1, P < 0.001); there was, however, no further stimulation of oxygen or glucose uptake compared with the control forearm. During the clamp, the ratio of glucose to oxygen uptake was similar in the control and in the infused forearms (0.27 +/- 0.11 and 0.23 +/- 0.09, respectively), and was not altered by adenosine (0.31 +/- 0.9 and 0.29 +/- 0.10). We conclude that in insulin-re15-76sistant patients with hypertension, adenosine-induced vasodilation recruits oxidative muscle tissues and exerts a modest, direct metabolic effect to promote muscle glucose uptake in the fasting state. Despite these effects, however, adenosine does not overcome muscle insulin resistance.

Hypertension-associated hypalgesia. Evidence in experimental animals and humans, pathophysiological mechanisms, and potential clinical consequences.

A behavioral hypalgesia (increased response threshold to noxious stimuli) has been consistently, although not invariably, reported in spontaneous and experimental acute and chronic hypertension in the rat. Studies in human hypertension have also demonstrated a diminished perception of pain, assessed as pain thresholds or ratings. The sensitivity to painful stimuli correlated inversely with blood pressure levels, and this relationship extended into the normotensive range. Evidence in humans and rats points to a role of the baroreflex system in modulating nociception. In the rat, blood pressure-related antinociception may be due to attenuated transmission of noxious stimuli at the spinal level secondary to descending inhibitory influences that are projected from brain stem sites involved in cardiovascular regulation and that may depend on baroreceptor activation and/ or on a central "drive." Both endorphinergic and noradrenergic central neurons (the latter acting through postsynaptic alpha 2-receptors) have been shown to be involved, and other mediators probably also play a role. Functionally, blood pressure-related antinociception may represent an aspect of a more-complex coordinated adaptive response of the body to "stressful" situations. It is still uncertain whether in human essential hypertension hypalgesia is secondary to elevated blood pressure or whether both depend on some common mechanism. Studies on the effect of hypotensive treatment are too few to allow conclusions. According to one hypothesis, the reduction in pain perception caused by baroreceptor activation secondary to blood pressure elevation may represent a rewarding mechanism that may be reinforced with repeated stress and may be involved in the development of hypertension in some individuals. Hypertension-associated hypalgesia may have clinically relevant consequences, especially in silent myocardial ischemia and unrecognized myocardial infarction, both of which are more prevalent in hypertensive individuals.

Arterial hypertension is associated with hypalgesia in humans.

An association between increased blood pressure and hypalgesia has been reported in several studies in animals and in a few reports in humans. We investigated the relationship between hypertension and pain perception by comparing the response to graded electrical stimulation of the tooth pulp, which is thought to represent an exclusively nociceptive system. The test was performed with a commercial tooth pulp tester in a large series of subjects with borderline or established hypertension and in three groups of normotensive controls: volunteers, nonhypertensive patients, and medical students with a well-established or no family history of hypertension. Subjects had to report when they started to feel pulp stimulation (sensory threshold) and when this became painful (pain threshold). Sensory and pain thresholds were obtained as means of the measurements on four healthy, unfilled teeth. Sensory thresholds were significantly higher in subjects with borderline or established hypertension than in two of the three normotensive groups (volunteers and normotensive patients), whereas no significant difference was observed between the two hypertensive groups. The results for the pain threshold were qualitatively similar but less clear and less amenable to statistical analysis because this parameter could not be determined with accuracy in a number of subjects in whom the subjective pain threshold was above the upper range of stimulation of the instrument. The association between blood pressure levels and pain perception was further confirmed by the highly significant correlation found for the overall data between mean arterial blood pressure and both thresholds.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired insulin action on skeletal muscle metabolism in essential hypertension.

Previous studies have shown that essential hypertension is frequently associated with insulin resistance. The tissues responsible for this metabolic alteration have not been defined. We tested the hypothesis that skeletal muscle is the site of insulin resistance of essential hypertension with the use of the perfused forearm technique. Eight hypertensive (age 42 +/- 3 years, body mass index 27 +/- 1 kg/m2, intra-arterial mean blood pressure 126 +/- 4 mm Hg) and seven normotensive (age 48 +/- 3 years, body mass index 26 +/- 1 kg/m2, mean blood pressure 95 +/- 4 mm Hg) male volunteers were studied. After glucose ingestion (40 g/m2), normal glucose tolerance in the patients was maintained at the expense of a heightened plasma insulin response, suggesting the presence of insulin resistance. During graded, local (intra-arterial) hyperinsulinemia encompassing the physiological range (12-120 milliunits/l), glucose uptake by forearm tissues was significantly (p less than 0.03) reduced in the hypertensive subjects as compared with the controls at each of five insulin steps, by 43% on the average. In addition, forearm lactate and pyruvate release were significantly less stimulated in the hypertensive than in the normotensive group (p less than 0.01 for both), presumably as a consequence of the decreased glucose influx. Forearm exchange of oxygen, carbon dioxide, lipid substrates (free fatty acids, glycerol, and beta-hydroxybutyrate), and potassium were similar in the hypertensive and normotensive groups in the basal state. Insulin had no effect on oxygen consumption, carbon dioxide production, and respiratory quotient in either study group, whereas it stimulated free fatty acids, glycerol, and potassium uptake to the same extent in the hypertensive and normotensive groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Seasonal influences on blood pressure in high normal to mild hypertensive range.

To investigate the seasonal influences on various arterial blood pressure measurements, 22 subjects in the high normal to mild hypertensive range were examined twice following the same protocol. In one group (13 subjects), measurements were first done in warm conditions and repeated 5-7 months later in cold conditions; in the second group (nine subjects) a reverse sequence was followed. Blood pressure was measured under casual conditions during a hand grip exercise test, mental arithmetic test, and submaximal multistage bicycle exercise test; during the following 24 hours, blood pressure was measured serially with a noninvasive ambulatory blood pressure recorder. Daily outdoor maximum and indoor laboratory temperatures were also obtained. In the cold season, significantly higher values (on the average by 5-10 mm Hg, p less than 0.01) were obtained in both groups for mean diastolic daytime blood pressure. For other measurements, a trend toward higher values in the cold season was observed in both groups, although statistical significance was not obtained in all instances. For nighttime measurements, irrespective of the seasonal sequence, lower values were observed in the second session. Significant correlations were found between the differences in the average daytime ambulatory blood pressures and the corresponding changes of daily maximum outdoor temperatures after 5-7 months. These observations indicate that arterial blood pressure may be strongly influenced by environmental temperature. This phenomenon should be taken into account both in the evaluation of the individual hypertensive patients and in the design and analysis of studies on arterial hypertension, especially when ambulatory blood pressure techniques are employed.

Effects of chronic angiotensin converting enzyme inhibition on glucose tolerance and insulin sensitivity in essential hypertension.

The relation between the renin-angiotensin-aldosterone (RAA) system and carbohydrate metabolism and insulin sensitivity in essential hypertension has not been investigated systematically. Twenty nondiabetic patients (age, 49 +/- 1 years; body mass index (BMI), 26.1 +/- 0.4 kg/m2) with essential hypertension (blood pressure, 155 +/- 3/105 +/- 1 mm Hg) received an oral glucose tolerance test (OGTT) at the end of a 1-month placebo period and again monthly during 3 months of angiotensin converting enzyme (ACE) inhibition (cilazapril, 5 mg/day). Furthermore, a two-step euglycemic insulin clamp was performed after placebo and again at the end of treatment. Blood pressure fell by 7 +/- 4/10 +/- 3 mm Hg (p less than 0.001), while BMI remained stable. On the euglycemic clamp, insulin-mediated (plasma insulin, 470 pM) whole body glucose use averaged 42.5 +/- 1.6 mumol.min-1.kg-1 before and 43.6 +/- 1.9 after ACE inhibition (p = NS). Substrate concentrations and oxidative rates and energy expenditure (as estimated by indirect calorimetry) were not altered by ACE inhibition, either in the fasting state or in response to insulin. In contrast, oral glucose tolerance was significantly (p less than 0.05) improved after treatment (area under OGTT curve (AUC), 240 +/- 24 versus 282 +/- 23 mmol 2 hr.l-1). The latter change was associated with enhanced (+16%, p less than 0.05) insulin responsiveness to glucose (estimated as the insulin AUC divided by the glucose AUC) throughout the 3 months of ACE inhibition. At baseline, both the OGTT and the clamp had a marked hypokalemic effect (mean decrements in plasma potassium of 0.75 +/- 0.05 and 0.92 +/- 0.05 mmol/l, respectively) in association with plasma aldosterone reductions of 30% and 50%. Chronic ACE inhibition caused a further 20% (p less than 0.03) lowering of plasma aldosterone concentrations but attenuated insulin-induced hypokalemia. Plasma sodium, which was unaltered by the pretreatment tests, fell during the posttreatment tests (by 3 mmol/l, p less than 0.001). In the urine, the ratio of the fractional excretion of potassium to that of sodium was decreased by both oral glucose (-22%, p less than 0.01) and ACE inhibition (-21%, p less than 0.001). Higher plasma potassium levels before treatment predicted a better blood pressure response to ACE inhibition (r = 0.60, p less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Renal scintigraphic captopril test in the diagnosis of renovascular hypertension.

Angiotensin converting enzyme (ACE) inhibitor-induced renal failure has been reported in bilateral renal artery stenosis and in stenosis in solitary kidneys, but not in unilateral renal artery stenosis. In these patients, however, a functional impairment of the kidney ipsilateral to the stenosis can often be detected after ACE inhibition by scintigraphic techniques employing glomerular radionuclide tracers like 99mTc-diethylenetriamine pentaacetic acid (DTPA). Dynamic renal scintigraphy with 99mTc-DTPA before and 1 hour after administration of captopril, 25 mg (renal scintigraphic captopril test; RSCT), was performed in a selected series of 39 hypertensive subjects with suspected renovascular hypertension. Changes in glomerular filtration rate induced by captopril on the individual kidney were estimated by assessing the early (120-180 seconds) DTPA uptake by the kidney. Values were expressed as the ratio between the kidney with the lower uptake and the contralateral one in 34 patients and as the ratio of the kidney counts to the injected dose in five patients with solitary kidneys, aortic coarctation, or both. Compared with precaptopril values, postcaptopril uptake decreased markedly in 14 subjects (-62.42 +/- 30.94 [SD]%; range, -25 to -100%) and decreased modestly or even increased in the other 25 (+0.57 +/- 9.83%; range, +28 to -13%). Of the 14 subjects considered to be RSCT-positive diagnostic workup revealed either established (10) or strongly suspected (2) renal artery stenosis in 12 and aortic coarctation in 2 subjects. In another patient with established renovascular hypertension, results of the RSCT were negative when performed in the supine position but became positive when repeated in the sitting position.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular filling: relationship with arterial blood pressure, left ventricular mass, age, heart rate and body build.

The relationships of age, heart rate, body build and, in particular, of arterial blood pressure and left ventricular mass to several Doppler indexes of diastolic function were evaluated in a series of 80 subjects with a wide range of blood pressure levels (106-217/68-144 mmHg). Body build and age results were inversely correlated to the indexes, reflecting the early contribution to left ventricular filling, whereas the increase in heart rate was associated with an increase in late diastolic contribution. Strong correlations (in most instances, P less than 0.0001) were observed with arterial blood pressure and left ventricular mass: the increase of these parameters was associated with a decrease of early transmitral peak velocity (E peak) and of early filling fraction, with an increase of late diastolic transmitral peak velocity (A peak) and of A:E ratio and, finally, with an increase of both deceleration time of E peak and acceleration time to A peak. Blood pressure or left ventricular mass were also confirmed as strong predictors of nearly all the Doppler-derived diastolic indexes by stepwise multiple regression analysis. When the subjects were subdivided into quintiles according to diastolic blood pressure and the average values of the five subgroups were compared, age, heart rate and body build results were similar in the quintiles while diastolic blood pressure increased stepwise by 10 mmHg. Analysis of variance showed significant differences for all the indexes of left ventricular filling except deceleration time of and acceleration time to E peak (P less than 0.05 to P less than 0.0001) and almost all the echo-Doppler indexes showed a linear trend with diastolic blood pressure and left ventricular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased circulating levels of ouabain-like factor in patients with asymptomatic left ventricular dysfunction.

BACKGROUND: Much evidence has been accumulated that human plasma contains digitalis-like factor(s) with Na/K ATPase inhibitor properties. Increased concentrations of ouabain-like factor (OLF) have been reported in patients with moderate to severe hypertension and in patients with overt congestive heart failure due to dilated cardiomyopathy. AIM: The presence of circulating OLF has not been investigated in borderline to mild hypertension or in the early stage of dilated cardiomyopathy. METHODS AND RESULTS: The study population consisted of 18 normal volunteers, 24 patients with borderline to mild hypertension, 47 patients with asymptomatic left ventricular dysfunction (ALVD) due to dilated cardiomyopathy and 26 patients with cardiac arrhythmias but normal left ventricular function. OLF values (pM ouabain equivalent) were assayed in extracted plasma, using a radioimmunoassay for ouabain. OLF was, respectively, 29.4+/-20.6 pM in normal controls, 39.1+/-23.8 pM in hypertensives, 35+/-18 pM in patients with cardiac arrhythmias, 52.3+/-25.8 pM in ALVD patients not treated with digoxin and 64.6+/-29.6 pM in ALVD patients treated with digoxin. Patients with ALVD, both treated and not treated with digoxin, had OLF significantly higher (P<0.05) than all the other groups. In patients with ALVD no correlation between OLF and left ventricular ejection fraction was observed. In the hypertensive group no correlation between OLF and both diastolic and systolic pressure was found. CONCLUSION: Increased concentrations of OLF were observed in patients with left ventricular dysfunction due to dilated cardiomyopathy, before the occurrence of overt heart failure, suggesting that OLF may be an early marker of the disease.

Different determinants of left ventricular filling in normotensive subjects and essential hypertensive patients.

The aim of the study was to evaluate the relationships between left ventricular (LV) filling and age, heart rate (HR), blood pressure (BP), and LV mass in three groups of subjects with different casual blood pressure. Twenty normotensive subjects (NT: age 39.2 +/- 7.2; BP 121.6 +/- 11.3/77.7 +/- 7.5 mm Hg), 16 borderline hypertensives (BH: age 38.6 +/- 9.2; BP 138.2 +/- 11.6/91.7 +/- 9.4 mm Hg), and 20 essential hypertensives (EH: age 44.5 +/- 8.3; BP 165.7 +/- 14.8/107.6 +/- 11.4 mm Hg) underwent 2D Echo evaluation and PW Doppler measurements of transmitral blood flow velocity. In NT, the Doppler indexes of LV filling showed significant correlations only with age and heart rate (age v E peak: r = .68 P less than .001; v A peak: r = .45, P less than .05; v A/E: r = .78, P less than .001. Heart rate v A peak: r = .78, P less than .001, v A/E: r = .74, P less than .001, respectively). Similar but weaker relationships were observed in BH. On the contrary, EH showed no significant correlations with age or heart rate, but with both systolic blood pressure (SBP), diastolic blood pressure (DBP), and LV mass (SBP v A peak: r = .49, P less than .05; v A/E: r = .68, P less than .001; DBP v E peak: r = 44, P less than .05; v A/E: r = .58, P less than .01. Left ventricular mass v E peak: r = .45, P less than .05; v A/E: r = .51, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

European Captopril Radionuclide Test Multicenter Study. Preliminary results. Inspective renographic analysis. The European Captopril Radionuclide Test Multicenter Study Group.

Captopril radionuclide test (CRT) has been introduced in clinical practice as a screening test for renovascular hypertension, since it allows the detection of the decrease of glomerular filtration rate that may be induced by angiotensin converting enzyme inhibition (25 mg oral captopril) in kidneys ipsilateral to a renal artery stenosis. However, due to the low prevalence of the disease, experiences in single centers may hardly satisfy the need for representative series of patients to validate the test. Nineteen centers participated in a collaborative study (CRT European Multicenter Study) that collected data from 424 patients. Here we report on the first results obtained by inspective renographic analysis. The captopril radionuclide test greatly potentiated the diagnostic performance of conventional renography and the accuracy was maximal when relying simply on postcaptopril findings alone. Specificity was 84.1% in the overall population and 91.8% in uncomplicated patients without nephropathy and renal insufficiency. Taking into account the sole arteriographic diagnosis, sensitivity was 73.2% or 90.7% for the subjects with unilateral or bilateral stenosis and an angiographic degree of stenosis greater than or equal to 70%. On the other hand, when a successful outcome of blood pressure after revascularization or nephrectomy was considered as the gold standard for the diagnosis of renovascular hypertension, a high sensitivity was obtained (92.7%). Moreover, the test became negative after intervention in the great majority (88%) of patients who had a positive preintervention CRT and a normalization of blood pressure after revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)

Echo-Doppler assessment of left ventricular filling in borderline hypertension.

The aim of this study was to evaluate left ventricular anatomy and diastolic function in borderline essential hypertension. To this aim, 16 borderline hypertensive patients underwent echocardiographic and pulsed-wave Doppler evaluation. As control groups, 20 normotensive controls and 20 patients with established hypertension were evaluated by the same procedure. By the Doppler assessment of transmitral blood flow, the following indices of left ventricular diastolic function were obtained: early (E) and late (A) peak flow velocity, late to early velocity ratio (A/E), early filling fraction (EFF) and acceleration and deceleration times of early and late flow peaks. Borderline hypertensives had an interventricular septum and posterior wall thickness significantly higher than normotensives and lower than established hypertensives. As regards the diastolic indexes, borderline hypertensive patients had significantly higher A peaks (P less than .02) and A/E ratios (P = .05) and lower EFF (P less than .02) as compared to normotensive controls. No significant differences were on the other hand observed with established hypertensive patients. This resultant diastolic pattern was independent of age, as indicated by the analysis of age-matched subgroups. The presence of diastolic function changes in borderline hypertension confirms the early appearance of this kind of abnormality in hypertensive heart disease. On the other hand, the finding of increased left ventricular wall thickness in borderline hypertensives does not allow us to conclude that, as suggested by other authors, diastolic function changes in the early stage of hypertension are independent on anatomical modifications.(ABSTRACT TRUNCATED AT 250 WORDS)

Microalbuminuria and casual and ambulatory blood pressure monitoring in normotensives and in patients with borderline and mild essential hypertension.

Several reports suggest that urinary albumin excretion may be elevated in patients with essential hypertension and that this index may be a good predictor for cardiovascular complications. The aim of this study was to compare 24-hour urinary albumin excretion in a group of normotensives, borderline, and untreated mild hypertertensives and to assess, in a subgroup of them, the possible relations between microalbuminuria and arterial blood pressure. Fifteen normotensives, 16 borderline, and 19 mild hypertensive patients were studied. Slightly but significantly higher values of microalbuminuria were observed in the mild hypertensives compared to the other two groups. In 21 borderline and mild hypertensive patients 24-hour microalbuminuria was related to casual blood pressure and noninvasive ambulatory blood pressure monitoring. A significant correlation was found between microalbuminuria and average day-time diastolic blood pressure. Our data suggest that albumin excretion is slightly increased in mild arterial essential hypertension; the direct association between microalbuminuria and arterial diastolic blood pressure during daily activities seems to confirm a pathophysiological link between transcapillary protein escape and arterial blood pressure that warrants further studies.

Reduced cardiovascular efficiency and increased reactivity during exercise in borderline and established hypertension.

In this study, exercise capacity was evaluated in patients with borderline and established, uncomplicated, essential hypertension as compared to normal subjects. To this aim, the response of blood pressure, heart rate and cardiac work to a multi-stage exercise test was investigated by analyzing the results of linear regression fitting of cardiovascular parameters (ie, heart rate, systolic blood pressure and rate-pressure product (RPP)) versus time of exercise. Compared to normal patients, both essential and borderline hypertensive patients had a shorter average duration of exercise test (ie, a decreased exercise capacity), always negative for transient myocardial ischemia. This was in spite of a mild increment of maximal RPP (+19% and +10% v normal patients, respectively). Reduction of exercise duration in borderline and established hypertensive patients was related to the higher RPP at rest (+26% and +56% related to normal patients, respectively) and to the steeper slopes (rates of increment) of heart rate systolic pressure and RPP during exercise. Interestingly, in the overall population of normal and hypertensive subjects, the slopes of heart rate and RPP were directly correlated with basal blood pressure. In conclusion, these data indicate a decreased exercise tolerance in both established and borderline hypertensive patients without documented myocardial ischemia. This abnormality, which appears to be due to a disproportional increment during exercise not only of systolic pressure but also of heart rate, could reflect abnormalities in the autonomic control of heart function.

Ultrasonic myocardial texture in hypertensive mild-to-moderate left ventricular hypertrophy: a videodensitometric study.

Myocardial texture analysis of two-dimensional echocardiographic gray level distribution is abnormal in hypertensive patients with severe increase of left ventricular mass. The aim of this study was to investigate the behavior of this parameter in hypertensive patients with absent-to-moderate left ventricular hypertrophy, more representative of the overall hypertensive population. We compared male essential hypertensive patients, with absent or mild-to-moderate left ventricular hypertrophy, with normotensive sedentary healthy subjects as controls. The groups (n = 18 each) were age- (+/- 2 years) and sex-matched. All subjects performed ambulatory blood pressure measurements for the evaluation of 24 h mean systolic and diastolic blood pressure. Quantitative analysis of echocardiographic digitized imaging was performed through a calibrated 256 gray level digitization system to calculate midseptum and midposterior end-diastolic and end-systolic first and second order textural analysis. In particular were observed the mean gray level cyclic variations to deriving the cyclic variation index (CVI). The hypertensives showed a significantly lower CVI compared with controls both for septum (P < .001) and for posterior wall (P < .0001). No significant relationships were found between CVI and relative diastolic thickness both of septum and posterior wall. Conversely, a significant inverse relationship was found between systolic arterial pressure values and CVI both of septum and posterior wall. Abnormalities of two dimensional echocardiographic gray level distribution are present also in hypertensive patients with absent or with mild-to-moderate levels of left ventricular hypertrophy, but seem unrelated to the degree of echocardiographic hypertrophy as such. Changes in collagen network distribution or microcirculatory alterations, secondary to pressure-volume overload per se or to other complex humoral factors, could explain these abnormalities. Further work is needed to establish the clinical, therapeutic, and prognostic implications of these findings.

Endogenous digitalislike factors in obstructive sleep apnea.

Recent studies have provided evidence that hypoxia may stimulate the release of endogenous digitalislike factors (EDLF). Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia during sleep and may be associated with sympathetic activation and a high risk of developing hypertension. This study was designed to measure EDLF in the plasma of patients with OSA diagnosed by polysomnography, with patients being classified by the number of apneic-hypopneic episodes/h sleep (apnea-hypopnea index, AHI). Plasma was obtained in the morning from 8 male normotensive OSA patients (OSA-N) (AHI 70+/-6), 2 untreated hypertensive OSA patients (OSA-HT), and 11 age-matched healthy male controls (C). EDLFs of different hydrophobicities were separated from the same plasma sample by solid-state C18-cartridges with 25% acetonitrile (ACN) (EDLF-1) followed by 40% ACN (EDLF-2). This procedure recovered ouabain in the first fraction and digoxin and digoxigenin in the second. EDLF was quantified in pM ouabain-equivalents by a human placenta radioreceptor assay. EDLF-1 levels were similar for OSA-N and C (231+/-55 vs. 258+/-58), whereas EDLF-2 levels were increased in OSA-N (244+/-51 vs. 110+/-25 in C, p=0.02). Norepinephrine was increased in apneics. The two OSA-HT had EDLF and norepinephrine levels similar to OSA-N. These preliminary results suggest that OSA is associated with an increase in the more hydrophobic EDLF levels in both normotensive and hypertensive states. No significant increase was found for the less hydrophobic ouabain-like EDLF.

Detection of digitalis compounds using a surface plasmon resonance-based biosensor.

An automated surface plasmon resonance-based biosensor system has been used to detect endogenous and exogenous digitalis-like factors (EDLF) in the pmolar range in real time. EDLF was purified from umbilical cord blood. EDLF has been suggested to play a role in hypertension and in perinatal adaptation. Highly specific polyclonal anti-ouabain antibodies showed a high affinity binding capacity for ouabain, ouabagenin and strophantidin with an IC50 value of 5 x 10(-10) M, 7.0 x 10(-10) M and 2 x 10(-8) M, respectively. EDLF cross-reacted with antibodies and its concentration in plasma at IC50 was around 50 pmol ouabain equivalent. This study shows the potential usefulness of the biosensor technology for biomolecular interaction analysis. The features of this technology (fully automated, measured in real time, sharpened response) offer several advantages compared with a traditional immunoassay like radioimmunoassay (RIA) in the detection of digitalis compounds in human fluids.