Aortic pulse wave velocity and HeartSCORE: improving cardiovascular risk stratification. a sub-analysis of the EDIVA (Estudo de DIstensibilidade VAscular) project.

BACKGROUND: HeartSCORE is a tool for assessing cardiovascular risk, basing its estimates on the relative weight of conventional cardiovascular risk factors. However, new markers of cardiovascular risk have been identified, such as aortic pulse wave velocity (PWV). The purpose of this study was to evaluate to what extent the incorporation of PWV in HeartSCORE increases its discriminative power of major cardiovascular events (MACE). METHODS AND RESULTS: This study is a sub-analysis of the EDIVA project, which is a prospective cohort, multicenter and observational study involving 2200 individuals of Portuguese nationality (1290 men and 910 women) aged between 18 and 91 years (mean 46.33 ± 13.76 years), with annual measurements of PWV (Complior). Only participants above 35 years old were included in the present re-analysis, resulting in a population of 1709 participants. All MACE - death, cerebrovascular accident, coronary accidents (coronary heart disease), peripheral arterial disease and renal failure - were recorded. During a mean follow-up period of 21.42 ± 10.76 months, there were 47 non-fatal MACE (2.1% of the sample). Cardiovascular risk was estimated in all patients based on the HeartSCORE risk factors. For the analysis, the refitted HeartSCORE and PWV were divided into three risk categories. The event-free survival at 2 years was 98.6%, 98.0% and 96.1%, respectively in the low-, intermediate- and high-risk categories of HeartSCORE (log-rank p < 0.001). The multi-adjusted hazard ratio (HR) per 1 - standard deviation (SD) of MACE was 1.86 (95% CI 1.37-2.53, p < 0.001) for PWV. The risk of MACE by tertiles of PWV and risk categories of the HeartSCORE increased linearly, and the risk was particularly more pronounced in the highest tertile of PWV for any category of the HeartSCORE, demonstrating an improvement in the prediction of cardiovascular risk. It was clearly depicted a high discriminative capacity of PWV even in groups of apparent intermediate cardiovascular risk. Measures of model fit, discrimination and calibration revealed an improvement in risk classification when PWV was added to the risk-factor model. The C statistics improved from 0.69 to 0.78 (adding PWV, p = 0.005). The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also determined, and indicated further evidence of improvements in discrimination of the outcome when including PWV in the risk-factor model (NRI = 0.265; IDI = 0.012). CONCLUSION: The results clearly illustrate the benefits of integrating PWV in the risk assessment strategies, as advocated by HeartSCORE, insofar as it contributes to a better discriminative capacity of global cardiovascular risk, particularly in individuals with low or moderate cardiovascular risk.

Renal and cardiovascular risk predictive value of two different microalbuminuria screening methods in patients with hypertension with/without diabetes in Portugal.

MicRoAlbuminuria sCreening survEy (RACE) was a multicentre, observational, cross-sectional study conducted in primary health-care settings of Portugal. Here, we present a post-hoc analysis from the RACE study, assessing the renal and cardiovascular (CV) risk predictive value of two different microalbuminuria (MA) screening methods, nephelometry with 24-h urine (MA-24 h) and Micral test with occasional urine (MicralA) in patients with hypertension (HTN) with/without type 2 diabetes mellitus (T2DM). Out of 3065 patients, 1173 (38.3%) were in the HTN group without T2DM (HTN) and 1892 (61.7%) in the HTN group with T2DM (HTN+T2DM). The overall prevalence of MA was 50.6% determined by MicralA and 22.1% with MA-24 h. Urinary albumin excretion data obtained by both techniques correlated significantly (rs=0.586; P<0.001). In all subjects, MicralA showed a sensitivity of 93%, specificity of 62% for detection of MA, with a positive predictive value of 41% and negative predictive value of 97%. With both methods, the presence of MA was independently associated with a higher risk (1.5- to 2.9-fold) of CV and renal organ damage in both HTN and HTN+T2DM groups. MicralA, due to its high sensitivity and negative predictive value, can be considered as a valid and reliable method for MA screening in patients with HTN with/without T2DM.

Bacterial mesosomes. Real structures or artifacts?

The ultrastructural study of membrane organization in gram-positive bacteria related to the OSO4 fixation conditions revealed that large, complex mesosomes are observed only when the bacteria are subjected to an initial fixation with 0.1%OSO4 in the culture broth, as in the prefixation step of the Ryter-Kellenberger procedure. Evidence was obtained suggesting that the large mesosomes are produced by this prefization. The kinetic study of the membrane morphological alterations occurring during the prefixation of Bacillus cereus with 0.1%OSO4 in the culture broth showed that the amount of mesosome material increases linearly from zero to a maximum observed at 1.7 min of prefixation and that at about this time a maximum is reached for the number of mesosomes per unity of cell area and for the average individual mesosome area. The large mesosomes observed in gram-positives fixed by the complete Ryter-Kellenberger procedure would be the result of the membrane-damaging action of 0.1%OSO4. Such damaging action was deduced from the observation thay 0.1%OSO4 quickly lyses protoplasts and induces a quick and extensive leakage of intracellular K+ from B. cereus and Streptococcus faecalis. In support of that interpretation is the observation that in bacteria subjected to several membrane-damaging treatments, mesosome-like structures are seen after three different fixation procedures. In bacteria initially fixed with 1% OSO4, 4% OSO4 or 2.5% glutaraldehyde, no large complex mesosomes are observed, small and simple invaginations of the cytoplasmic membrane being present. The size of these minute mesosomes is inversely proportional that causes of fixation. Uranyl acetate was found among the studied fixatives the one to the rate the least damage to bacterial membranes. This fixative satisfactorily preserves protoplasts. In bacteria initially fixed with uranyl acetate no mesosomes were found. The results of the present work throw serious doubts on the existence of mesosomes, both large and small, as real structures of bacterial cells. It is proposed that a continuous cytoplasmic membrane without infoldings (mesosomes) would be the real pattern of membrane organization in gram-positives.

Correlates of plasma atrial natriuretic factor in health and hypertension.

Plasma concentrations of atrial natriuretic factor (ANF) were compared in normotensive subjects and subjects with untreated, uncomplicated essential hypertension (n = 21 pairs) matched for age, sex, and race. Plasma peptide values were slightly greater (45 +/- 3 vs 36 +/- 3 pg/ml; p less than 0.05) in the hypertensive group. On univariate analysis, age (r = 0.52, n = 47, p less than 0.001) and creatinine clearance (r = -0.30, n = 47, p less than 0.05) were significantly related to plasma ANF concentrations, but arterial pressure was not (r = 0.14, n = 47), in an extended group of normal subjects. In contrast, plasma ANF values were related to arterial pressure in both an extended group of subjects with untreated essential hypertension (r = 0.54, n = 38, p less than 0.001) and in our total heterogeneous pool of hypertensive patients (r = 0.46, n = 79, p less than 0.001), but weak positive associations with age and inverse relationships with creatinine clearance were not statistically significant in either hypertensive group. Similar weak inverse relationships between plasma ANF values and renin-angiotensin-aldosterone system activity were found in both normal and hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptides and renin release.

The relationship between endogenous plasma concentrations of atrial natriuretic peptide and renin was examined in resting normal subjects and patients with cardiac impairment. To test the hypothesis that atrial natriuretic peptide inhibits renin secretion, intravenous infusions of atrial natriuretic peptide were administered to normal volunteers, patients with end-stage renal failure, and conscious dogs in both sodium-replete and sodium-depleted states. Plasma atrial natriuretic peptide and renin were inversely related in normal subjects (r = -0.52, n = 140, p less than 0.001), but a weak positive association between these two variables was observed in patients with cardiac impairment (r = 0.32, n = 60, p less than 0.02). Low doses of both 26- and 28-amino-acid human atrial natriuretic peptide (2 pmol/kg/minute for two hours) given to sodium-replete normal subjects halved plasma renin compared with time-matched placebo values (19 +/- 4 and 18 +/- 3 versus 36 +/- 8 microU/ml, p less than 0.001 for both). Incremental doses of synthetic atrial natriuretic peptide suppressed plasma renin below time-matched placebo values in both sodium-replete (maximal suppression 1.2 +/- 0.4 versus 8.6 +/- 1.4 microU/ml, p less than 0.001) and sodium-depleted (maximal suppression 18.9 +/- 4.9 versus 51 +/- 13 microU/ml, p less than 0.05) dogs. This effect was initially apparent at low doses of atrial natriuretic peptide (1 pmol/kg/minute), and renin suppression was maximal, in both states, with lesser doses of atrial natriuretic peptide than those at which maximal natriuresis was observed. Atrial natriuretic peptide administered to patients with end-stage renal failure (10 pmol/kg/minute for one hour) caused no change in plasma renin. These data confirm that atrial natriuretic peptide inhibits renin secretion in a dose-related manner and suggest that this action of the peptide is modified by both the baseline sodium status and renal function of the recipient.

Influence of sublingual captopril on plasma catecholamine levels during hypertensive emergencies and cold immersion.

Experimental evidence of captopril-induced inhibition of sympathetic activity, mediated by decrease in angiotensin II production, is presented. The blood pressure, plasma catecholamine, plasma renin activity, and plasma aldosterone responses to a single dose of sublingual captopril in 23 patients with hypertensive emergencies were evaluated. The major correlation found was between the captopril-induced decrease in blood pressure and the decrease in plasma norepinephrine levels (r = 0.57, p less than 0.01). In another 11 hypertensive patients with normal or high renin levels, captopril lowered by 65 percent the increase in plasma norepinephrine induced by cold immersion of the forearm. In both circumstances, plasma renin and aldosterone levels changed in accordance with the expected inhibition of angiotensin converting enzyme activity. These data suggest that, in selected circumstances in hypertensive patients, captopril exhibits a depressive influence on sympathetic activity along with the inhibition of the renin-angiotensin system.

Accuracy of twenty-four-hour ambulatory blood pressure monitoring (night-day values) for the diagnosis of secondary hypertension.

OBJECTIVES: To determine the accuracy of 24-h ambulatory blood pressure monitoring, using the relationship between night-time and daytime values, in diagnosing secondary hypertension. PATIENTS AND METHODS: A prospective study was performed in a referred population of 402 hypertensive patients (clinic systolic/diastolic blood pressure > 140/90 mmHg). The ambulatory monitoring data included 24-h mean, awake (daytime) and sleeping (night-time) values. Secondary hypertension was diagnosed by standard procedures. To describe the accuracy of ambulatory blood pressure monitoring, receiver-operator characteristic curves were constructed, using sensitivity and specificity values for deciles of the distribution of overnight blood pressure falls (absolute and percentage). Measurements included the fall in nocturnal blood pressure, sensitivity (the percentage of those with secondary hypertension who were classified as non-dippers), specificity (the percentage of non-secondary hypertensives who were classified as dippers) and predictive values of ambulatory blood pressure monitoring. RESULTS: On average, overnight systolic/diastolic blood pressure fell in primary hypertensives (n = 290) by 20/18 mmHg (13%/19%), in white-coat hypertensives (n = 65, daytime ambulatory blood pressure <135/87 mmHg) by 17/15 mmHg (13%/19%) and in patients with secondary hypertension (n = 47, renal/renovascular and endocrine forms) by 13/11 mmHg (9%/12%). From receiver-operator characteristic curves, the nocturnal blood pressure fall of 15 mmHg showed the highest accuracy, with a sensitivity/specificity of 61%/69% (systolic) and 75%/62% (diastolic) whereas 10% (systolic) and 15% (diastolic) nocturnal falls had a sensitivity/specificity of 62%/74% (systolic) and 62%/70% (diastolic). The ambulatory blood pressure data had a high (>93%) negative predictive value for secondary hypertension. CONCLUSIONS: Secondary hypertension is associated with a blunted nocturnal fall in blood pressure. Ambulatory blood pressure monitoring data are not critically important for the diagnosis and screening of secondary hypertension but may be helpful in excluding it.

Deficiency of renal dopaminergic-dependent natriuretic response to acute sodium load in black salt-sensitive subjects in contrast to salt-resistant subjects.

OBJECTIVE: To evaluate the involvement of the renal dopaminergic system in the natriuretic responses to acute saline load in salt-resistant (SR) and salt-sensitive (SS) black normotensive (NT) and hypertensive (HT) subjects. DESIGN AND METHODS: We studied the relationship between the urinary excretion of dopa, dopamine (DA) and its metabolite DOPAC and the natriuretic responses to acute volume expansion (2 l NaCl 0.9% over 2 h) in 20 black NT subjects (12 SR and 8 SS) and 19 black HT subjects (10 SS and 9 SR). Subjects received a low salt (LS) diet (40 mmol sodium/day) for 1 week and a high salt (HS) diet (300 mmol sodium/day) for 1 week; the sequence of the dietary regimens was randomized. Comparisons were made between the results before the saline infusion (baseline) and the results 2 h after the infusion. RESULTS: In all the groups saline infusion induced significant increases in urinary volume (ml/4 h) of two- to three-fold and in urinary sodium excretion (mmol/4 h) of three- to ten-fold; these increases were significantly greater during the HS diet than during the LS diet. Saline infusion significantly increased the mean arterial pressure (MAP) by 5 mmHg in HT-SS subjects and by 4-5 mmHg in NT-SS subjects, but the MAP did not changed in the NT-SR and HT-SR groups. Under the LS diet, saline infusion changed the DA excretion (in nmol/4 h) by -49+/-89 in HT-SS subjects, by 17+/-52 in NT-SS subjects, by 235+/-72 in HT-SR subjects and by 220+/-86 in NT-SR subjects (P < 0.05 between SR and SS subjects). The saline infusion-induced changes in DA excretion correlated significantly with the increases in urinary sodium excretion (r = 0.71, P < 0.01) in the NT-SR and HT-SR subjects under the LS diet, but not in the SR groups on the HS diet nor in the SS groups (HT and NT) on either diet. Saline infusion significantly reduced the DA/dopa ratio in SS (NT and HT) but not SR (NT and HT) subjects, whereas the DA/DOPAC (dihydroxyphenylacetic acid) ratios were similar in all the groups. CONCLUSIONS: The urinary dopaminergic system may participate in the natriuretic responses to acute sodium load only in SR subjects (NT and HT) and only under LS diets, but not in SS subjects (NT and HT). This strongly suggests that black NT- and HT-SS subjects have an underlying impairment in the activity of the renal dopaminergic system which may be associated with a reduced decarboxylation of dopa into DA.

Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.

OBJECTIVE: To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension. DESIGN AND METHODS: In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60 mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24h ambulatory monitoring. RESULTS: Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen. CONCLUSIONS: Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.

Long-term administration of 1,3-dipropyl-8-sulfophenylxanthine causes arterial hypertension.

Adenosine has been shown recently to be the main factor responsible for the trophic effects of sympathetic innervation. As sympathetic denervation causes hypertrophic and hyperplastic changes reminiscent of those occurring in blood vessels of spontaneously hypertensive rats, we decided to study the effect of a continuous blockade of adenosine receptors on both blood vessel structure and blood pressure. A continuous infusion of 1,3-dipropyl-8-sulfophenylxanthine (DPSPX; 30 micrograms/kg per h for 7 days) to Wistar rats caused hyperplastic changes in peritoneal fibroblasts and mesenteric arterioles, hypertrophic changes in the smooth muscle of the tail artery and significant increase in the size of left ventricle myocardial cell nuclei. Both diastolic and systolic blood pressure increased significantly above control values. The results confirmed the trophic effects of adenosine and showed that chronic blockade of adenosine receptors causes arterial hypertension.

Preparation and pharmacological activity of the condensation product of adrenaline with acetaldehyde.

In vitro incubation of adrenaline with acetaldehyde resulted in the formation of an amorphous product (MA 3) which gave origin to two spots on chromatography plates. Preparative TLC allowed us to separate the corresponding substances, MA 4 and MA 5. Gas chromatography-mass spectrometry, ultraviolet and infrared spectra of MA 4 agree with the structure corresponding to 1,2-dimethyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline. MA 5 is very unstable and was not further characterized. Pharmacological experiments were carried out with MA 3 and MA 4 (and in some cases, MA 5) on isolated saphenous vein strips and isolated guinea-pig atria; responses of the nictitating membrane, blood pressure and hind-limb perfusion pressure were obtained in the anaesthetized dog. There were only quantitative differences between the effects of MA 3, MA 4 and MA 5 (where tested). Therefore, these effects are described as effects of TIQs (tetrahydroisoquinolines). TIQs contracted isolated saphenous vein strips, behaving as total agonists; the dose-response curves were displaced to the right by phentolamine and to the left by cocaine (potentiation factor: 2.7 +/- 0.1). In the dog, contractions of the nictitating membrane, rises of blood pressure and of the perfusion pressure (after i.a. injection) were observed. On isolated guinea-pig atria, weak beta adrenergic receptor activation was found. With higher concentrations, beta receptor blockade was observed, for both cardiac and vascular smooth muscle receptors. The effects of TIQs were short-lasting, showing that a rapid inactivation occured both in vitro and in vivo; neuronal uptake appears to play an important role in inactivation, since cocaine was able to block about 70% of the inactivation capacity of isolated vein strips. The effects of nerve stimulation on the vein strips or on the nictitating membrane were reduced by TIQs; however, this did not affect responses to noradrenaline and enhanced those to tyramine or DMPP. Simultaneously with reduction of the effects of electrical stimulation, blockade of inactivation of endogenous and exogenous noradrenaline was induced by TIQs. Marked depletion of noradrenaline levels in the heart, hypothalamus and aorta of the guinea pig was caused by MA 3 (1-3 mg/kg). It is concluded that the condensation products of adrenaline with acetaldehyde are not devoid of pharmacological activity, are taken up by adrenergic nerve terminals and may act as false transmitters. The similarity of effects of TIQs and acetaldehyde suggests that formation of TIQs may occur in vivo, after acetaldehyde (or ethanol) administration, both in the adrenal gland and in sympathetic nerve terminals. These TIQ alkaloids could play an important role in alcoholic intoxication and in the ethanol withdrawal syndrome.

Sympathetic denervation causes atrial natriuretic peptide-storing granules to appear in the ventricular myocardium of the rat.

Sympathetic denervation of the rat heart was produced by 6-hydroxydopamine. In denervated ventricles abundant "atrial" granules were observed whereas in controls no such granules were seen. Denervated ventricles and atria showed a very high content of atrial natriuretic peptide-like immunoreactivity (greater than 10 times higher than in control animals). We suggest that the sympathetic nervous system exerts a repressive effect upon synthesis of atrial natriuretic peptide-like material and upon the formation of atrial natriuretic peptide-storing granules in the ventricular myocardium.

Measurement of trough-to-peak ratios of four anti-hypertensive drugs on the basis of 24 h ambulatory blood pressure monitoring: different methods may give different results.

With 24 h ambulatory blood pressure monitoring (ABPM), the trough-to-peak (T/P) ratios (corrected for placebo) of atenolol 100 mg, cilazapril 2.5 mg, enalapril 20 mg and nifedipine-GITS 30 mg administered once daily for 4 weeks were determined in four groups of hypertensive patients. T/P ratios were calculated by three different methods: directly from the curves that averaged all individual 24 h profiles (A); averaging all individual T/P ratios after ABPM data were averaged for each patient over either 1 h intervals (B) or 3 h intervals (C). Methods B and C produced different values of T/P which, for each drug, were significantly higher with method C. With method A, nifedipine appeared to have the higher T/P. With methods B and C (which in contrast to method A, permitted statistical comparisons), differences between nifedipine and the other drugs were not significant. Meanwhile, method B appears to adhere most closely to FDA guidelines by taking more into account the interindividual variability of BP profile. Thus, we suggest that precise guidelines for measuring T/P on the basis of ABPM are needed, whereas for the comparison between drugs, both the mean value of the T/P and its variance must be determined.

Efficacy of captopril and nifedipine in black and white patients with hypertensive crisis.

We examined the antihypertensive efficacy of: (1) sublingual-oral single doses of captopril (25 mg) and nifedipine-capsules (10 mg) in 9 + 9 white patients and in 9 + 8 black patients with hypertensive crisis; and (2) a single oral dose of the slow-acting preparation of nifedipine-retard (20 mg) in another 10 black patients. Blood pressure (BP) was assessed at 10 min intervals for 6 h after administration. After 6 h, the BP falls induced by these drugs were still significantly lower than the baseline placebo values. Hypotensive effect of nifedipine-capsules was established more rapidly than that of captopril in both white and black patients, and of nifedipine-retard in black patients. Considering the area under the curve of BP values during the 6-h treatment, the overall hypotensive effect of nifedipine-capsules was similar to captopril in white patients, but significantly more pronounced than captopril and nifedipine-retard in black patients. In white patients similar maximal drops of BP (mean+/-s.e.m.) were obtained with nifedipine-capsules (71+/-4/52+/-4 mm Hg) and with captopril (69+/-4/50+/-3 mm Hg). In black patients the maximal drop of BP of nifedipine-capsules (70+/-4/52+/-4 mm Hg) was greater (P < 0.02) than that of captopril (48+/-4/32+/-3 mm Hg) but similar to that of nifedipine-retard (71+/-4/49+/-4 mm Hg). However, in contrast to nifedipine-capsules and captopril, nifedipine-retard produced a slower drop in BP. The time of peak drop in BP of both nifedipine-capsules and captopril occurred within the first 2 h whereas with nifedipine-retard it occurred only between 4 and 6 h after administration. Fewer patients reported side effects with nifedipine-retard as compared with the other two preparations. We conclude that single doses of captopril and nifedipine reduces BP for at least 6 h in both white and black patients with hypertensive crisis, but nifedipine is more potent than captopril in black patients. The slow release form of nifedipine-retard effectively and safely lowers BP while achieving a rapid enough effect without the critical rapid falls in BP that occur with nifedipine-capsules.

Brain natriuretic peptide as a marker of cardiac involvement in hypertension.

Hypertensive patients with heart abnormalities have increased risk of cardiovascular events. Brain natriuretic peptide is a natriuretic peptide mainly of ventricular origin produced in response to pressure and stretch. We hypothesise that brain natriuretic peptide could be a useful marker of cardiac remodelling in hypertensive patients. We studied 36 consecutive community mild-to-moderate hypertensive patients and 11 well-matched normotensive controls with respect to clinical characteristics, brain natriuretic peptide, creatinine and echocardiography parameters (M-mode, 2-D arid transmitral pulsed Doppler). Brain natriuretic peptide levels were significantly higher in hypertensive patients than in controls [36.54 (IQR: 38.61) vs. 10.30 (IQR: 13.20) pg ml(-1), p<0.0001] and it was correlated with left ventricular mass index. Hypertensive patients with impairment of diastolic filling had significantly higher brain natriuretic peptide concentrations than patients with no abnormalities on echocardiography [61.16 (45.38) vs. 31.27 (18.10) pg ml(-1), p=0.001]. Multivariate analysis showed that only diastolic dysfunction and left ventricular mass index were significantly and independently related with brain natriuretic peptide concentrations in this population. In conclusion, impairment of diastolic function and left ventricular mass index are related to brain natriuretic peptide levels, thus giving the insight that this peptide can be a marker of ventricular remodelling in hypertensive patients.

Differences in behavior profile between normotensive subjects and patients with white-coat and sustained hypertension.

It has been hypothesized that white-coat hypertensives (WCHs) have lower cardiovascular risk than sustained hypertensives (HTs), but higher emotional reactivity. We evaluated 92 HT patients (clinic and daytime BP>140/90 mmHg), 52 WCHs (clinic BP>140190 and ambulatory daytime BP<134/ 85 mmHg), and 74 normotensive subjects (NTs, clinic BP<140/90 and ambulatory daytime BP<134/85 mmHg), aged between 24 and 72 years, and matched for educational level, age, gender, and weight for depression, psychopathology, well-being, and quality of life. HTs showed worse scores than WCHs and NTs on most of the psychological variables; no differences were found between WCHs and NTs except on physical mobility. Daytime BP variability was HTs>WCHs>NTs, whereas nighttime BP variability was HTs>WCHs=NTs. We conclude that HTs have worse psychological profiles than the other two groups. WCHs and NTs have similar psychological profiles, although WCHs have a higher daytime BP variability, which is not associated with higher emotional reactivity.

Isolation of pinastric acid and ergosterol from Parmelia caperata (L.) Arch.

Among other common compounds, pinastric acid and ergosterol were isolated for the first time from Parmelia caperata. The isolation of these compounds is described; identification was made from the melting point and UV, IR, and mass spectral data.

Pharmacological characterization of postsynaptic alpha-adrenoceptor subtypes in five different dog arteries in-vitro.

The responses of helically cut strips of arteries isolated from five different sites in the body of dogs to relatively selective alpha 1- and alpha 2-adrenoceptor agonists and the antagonism exerted on these responses by relatively selective alpha 1- and alpha 2-adrenoceptor blockers have been studied. On all arteries (renal, splenic, cranial mesenteric, jejunal and femoral) phenylephrine was a full agonist whereas UK-14,304 was a partial agonist causing maximal contractions of 49, 30, 27, 27 and 10% of the maximum, respectively. Phenylephrine was more potent than UK-14,304, being 9 times more potent in the renal artery and up to 42 times more potent in the cranial mesenteric artery. In the dog saphenous vein, where there are both alpha 1- and alpha 2-adrenoceptors, it has been previously shown that UK-14,304 is 530 times more potent than phenylephrine. Prazosin in low concentrations displaced concentration-response curves for both phenylephrine and UK-14,304 (pA2 values of 8.16-8.43 and 8.13-8.79, respectively) whereas yohimbine was much less potent (pA2 values of 6.53-6.88 and 6.50-7.20, respectively). The results suggest that the alpha-adrenoceptors of all arteries studied are predominantly, if not exclusively, of the alpha 1-subtype.

Arterial distensibility in subjects with white-coat hypertension with and without diabetes or dyslipidaemia: comparison with normotensives and sustained hypertensives.

BACKGROUND: Arterial distensibility can be assessed by measuring pulse-wave velocity (PWV). OBJECTIVE: To determine whether diabetes, smoking and dyslipidaemia were associated with greater than normal stiffness of aortic walls in subjects with white-coat hypertension. METHODS: Arterial distensibility was assessed by automatic measurement of carotid-femoral PWV in 35 healthy normotensives, 46 white-coat hypertensives (WCH, clinic blood pressures >140/90 mm Hg, daytime blood pressures <130/85 mm Hg) and 81 ambulatory hypertensives (clinic blood pressures >140/90 mmHg, daytime blood pressures > or =130 mm Hg systolic or > or =85 mm Hg diastolic, or both) all matched for age, sex and body mass index. Nineteen normotensives (subgroup A), 28 WCH (subgroup A) and 37 ambulatory hypertensives (subgroup A) had only one or no other major cardiovascular risk factor whereas 16 normotensives (subgroup B), 18 WCH (subgroup B) and 44 ambulatory hypertensives (subgroup B) had also some combination of non-insulin-dependent diabetes, a smoking habit and dyslipidaemia. RESULTS: Both for the WCH and for ambulatory hypertensives diabetes and dyslipidaemia (subgroups B) were associated with higher (P<0.04) PWV (11.6+/-0.3 and 12.8+/-0.3m/s, respectively) than for subgroups A (9.3+/-0.5 and 10.9+/-0.6 m/s, respectively). In contrast, PWV for WCH in subgroup A (9.3+/-0.5m/s) did not differ (P>0.35) from those for the normotensive subgroups A (9.2+/-0.3m/s) and B (9.6+/-0.4m/s). PWV was not correlated to levels of glycaemia, glycosylated haemoglobin and cholesterolaemia. CONCLUSIONS: These results suggest that, both for ambulatory hypertensives and for WCH, diabetes and dyslipidaemia are associated with an impairment of arterial distensibility that can entail a greater than normal cardiovascular risk, which might dictate a more than usually stringent treatment of concomitant risk factors and possibly of high blood pressure. In contrast, PWV in WCH of the subgroup A did not differ from those in normotensives, reinforcing the hypothesis that WCH is associated with a benign cardiovascular outcome in the absence of other cardiovascular risk factors.

Low-dose oral contraceptives and 24-hour ambulatory blood pressure.

OBJECTIVE: To evaluate in normotensive women the influence of low-dose oral contraceptives (OC, monophasic formulations containing 30 microg of estrogen) on 24-h blood pressure. METHODS: We evaluated prospectively in 15 normotensive healthy women (three smokers) the influence of OC on 24-h ambulatory blood pressure monitoring (ABPM). ABPM was performed (SpaceLabs 90207) before and after 6-9 months of use of OC. We also evaluated ABPM in eight women (two smokers) before and after 6-8 months on an intrauterine device (IUD) as contraceptive method--these were used as control subjects. RESULTS: OC produced a significant increase in 24-h ABPM values (from 120+/-3/75+/-2 to 128+/-4/81+/-2 mmHg, P < 0.04) which was particularly evident for night-time values (from 108+/-2/64+/-2 to 120+/-4/73+/-2 mmHg, P < 0.02). After OC, two normotensive women developed 'hypertensive values'. In OC users there was a slight but significant increase in body weight which did not correlate with the increase of blood pressure. In contrast, in the control group (IUD) neither ABPM values nor weight were modified by the contraceptive maneuver. CONCLUSIONS: In normotensive women, low-dose OC may increase blood pressure to an extent that, at least in some women, may affect blood pressure control towards 'hypertensive values'. This stresses the importance of monitoring blood pressure values during OC treatment.