Grazia Covi

Autonomic system activity and 24-hour blood pressure variations in subjects with normal- and high-tension glaucoma.

PurposeAs suggested by findings of abnormal responses to posture in patients with normal-tension glaucoma (NTG), cardiovascular autoregulation may also be defective in primary open-angle glaucoma (POAG). Patients and MethodsBoth 24-hour ambulatory blood pressure monitoring and the head-up tilt test were performed in 17 subjects with NTG and in 13 subjects with high-tension POAG (ht-POAG). These groups were compared with 17 age-matched healthy individuals. Subjects undergoing cardiovascular therapy were excluded. ResultsNo significant differences in diurnal and nocturnal blood pressure and heart rate were found between the groups. A significant reduction in diurnal heart rate variability was found in NTG (12.1 ± 2.8 bpm) compared with the ht-POAG (15.0 ± 2.4 bpm, P < 0.01) and control groups (15.8 ± 3.0 bpm, P = 0.01]). Nocturnal diastolic blood pressure variability was also reduced in NTG (6.9 ± 2.2 mm Hg) compared with controls (8.6 ± 2.3 mm Hg, P < 0.05]) as was heart rate variability (6.3 ± 1.4 vs 8.3 ± 2.6 in ht-POAG, P < 0.05), suggesting blunted blood pressure and heart rate modulation in NTG subjects. Spectral analysis of short-term heart rate variability showed a significant reduction of total power in the supine position (1064 ± 600 in NTG vs 1688 ± 889 ms2 in controls, P < 0.05]). This was not accompanied either by a physiological reduction in total power or in a high-frequency component during the passive orthostatic stimulus. These differences tend to become more prominent in the clinically more severe forms of NTG (as identified by scores based on the extent of optic disk excavation, visual field damage, and progression of disease). This would suggest a correlation between the extent of autonomic disorder and severity of glaucoma. The &agr; index (root-square of low-frequency heart rate to low-frequency blood pressure ratio) was lower in the supine position in NTG subjects (8.1 ± 3.1 vs 10.6 ± 3.3 ms/mm Hg in controls, P < 0.05), confirming the reduced baroreflex sensitivity. ConclusionsThe results confirm the hypothesis that dysfunction of autonomic control of the cardiovascular response may be a contributing pathogenetic factor in NTG, inducing a chronic ischemia of the optic nerve.

Non-invasive detection of early endothelial dysfunction in hypercholesterolaemic subjects

Hypercholesterolaemia is associated with accelerated atherogenesis. Before the evidence of morphological lesions or plaques, endothelial dysfunctions, such as impairment in endothelium-dependent vascular tone regulation, may occur. We studied 32 subjects, 16 with primary hypercholesterolaemia and 16 normocholesterolaemic controls. Flow-dependent vasodilation, an endothelium-dependent phenomenon, was evaluated by measuring femoral artery diameter and flow velocity in basal conditions and during distal post-ischemic hyperaemia, using a high resolution echo-Doppler. Arterial distensibility and compliance were evaluated for the common carotid and femoral arteries, using a pulsed echo-tracking system and measuring the absolute and relative stroke change in arterial diameter. In the hypercholesterolaemic group there was no flow-dependent arterial relaxation, indicated by the area under the curve of percentage diameter variation as a function of time. This parameter was inversely correlated with both total and LDL-cholesterol values in all population subjects. No difference was observed between the two groups in endothelium-independent vasodilation induced by glyceryl trinitrate administration or arterial wall distensibility and compliance, confirming the hypothesis of a functional defect.

The effects of thromboxane A2 inhibition (Picotamide) and angiotensin II receptor blockade (Losartan) in primary Raynaud's phenomenon

Pancera P, Sansone S, Secchi S, Covi G, Lechi A (University of Verona, Verona, Italy). The effects of thromboxane A2 inhibition (Picotamide) and angiotensin II receptor blockade (Losartan) in primary Raynauds phenomenon. J Intern Med 1997; 242: 373–6.

Altered excretion of prostaglandin and thromboxane metabolites in pregnancy-induced hypertension.

The renal and systemic metabolites (the latter as 2,3-dinor derivatives) of prostacyclin and thromboxane A2 were measured, along with renal prostaglandin E2 and kallikrein, in the urine of 15 patients with pregnancy-induced hypertension, 15 normotensive pregnant women matched for both age and gestational age, and 15 normotensive nonpregnant control women. Urinary excretion of all prostaglandin and thromboxane metabolites studied proved significantly higher in normotensive pregnant women than in controls. Prostaglandin E2, 6-keto-prostaglandin F1 alpha, and 2,3-dinor-6-keto-prostaglandin F1 alpha were significantly lower in pregnancy-induced hypertensive women than in normotensive pregnant women, whereas thromboxane B2 and 2,3-dinor-thromboxane B2 showed no significant differences in the two groups. A significant negative correlation (r = -0.636, p less than 0.01) was found between urinary 2,3-dinor-6-keto-prostaglandin F1 alpha and mean blood pressure in the two groups of pregnant women taken as a whole. These data indicate that, in pregnancy-induced hypertension, there is an imbalance between vasodilator and vasoconstrictor factors, not only in the kidneys, but also at the systemic vascular level. This imbalance, which may in itself produce vasoconstriction, may also potentiate the hypertensive effect of catecholamines and angiotensin II.

Effect of losartan on heart rate and blood pressure variability during tilt test and trinitroglycerine vasodilation

OBJECTIVE To define the changes in variability of heart rate and of blood pressure during vasodilation in a group of hypertensive patients treated with an angiotensin II type I (AT1) receptor inhibitor. DESIGN Losartan (50 mg/day at 0800 h) or placebo were administered for 3 weeks according to a single blind, crossover, randomized protocol, to 18 hypertensive patients (16 men and two women, mean age 42 + 3.6 years). Continuous ECG recording and beat-to-beat blood pressure monitoring were carried out with subjects in the supine position and during a head-up tilt test, as well as after sublingual administration of trinitroglycerine. The elaboration of ECG traces in the frequency domain, was carried out using an autoregressive method and measured using the autoregressive moving average technique. RESULTS Orthostatic stimulus, both during treatment with losartan and with placebo, caused a significant decrease in the heart rate high frequency power; on the other hand, the low frequency power appeared unchanged after placebo and was significantly reduced with losartan. Five minutes after the administration of trinitroglycerine, the low frequency power with placebo showed a significant increase (817 -+ 221 versus 465 + 101 ms2, P < 0.03). No change was recorded in total power nor in low frequency or high frequency power during losartan therapy. The ratio of low frequency to high frequency powers showed a sympathetic prevalence during vasodilation only during placebo treatment, whereas a mainly unchanged balance was maintained during losartan treatment Blood pressure variability showed a sympathetic prevalence after upright and trinitroglycerine stimulation only in placebo-treated subjects. CONCLUSIONS Our study demonstrated that vasodilation is not able to evoke an unbalancing of the autonomic modulation in hypertensive patients treated with an AT1 receptor inhibitor, but permits the maintenance of a significant vagal component, thus highlighting the favorable profile of this drug in the autonomic control of circulation.

Early regression of left ventricular diastolic abnormalities in hypertensive patients treated with nifedipine

SummaryThe effects of nifedipine on blood pressure (BP), left ventricular hypertrophy, and diastolic function were evaluated in 14 patients with essential hypertension (EH). All males with a mean age of 44±6 years (range 35–58 years), and in ten normotensive subjects (control group) aged 32–42 years (mean age 36±4). A complete echocardiogram (ECHO) was performed in basal conditions after 1 and 6 months of therapy with nifedipine (20–40 mg/day). Left ventricular echocardiograms (LV ECHO, M-mode, two-dimensional guided) were plotted with a simultaneous ECG tracing by means of a computerized system that allows evaluation of the following parameters: LV end-diastolic and systolic diameters (EDD, ESD); variations in LV diameter and volume during the entire cardiac cycle, and the velocities of such variations; end-diastolic thicknesses of the interventricular septum and posterior wall (ST, PWT); LV mass, mass/volume (M/V) index, end-diastolic diameter/thickness (D/Th) index, and LV ejection fraction (EF). Left ventricular volume curves were obtained and the contributions of rapid filling (RF) and atrial systole (AS) to EDV were evaluated. Filling velocities during RF (vRF) and AS (vAS) were estimated, as well as the isovolumic relaxation period (IR).No significant changes were observed in the heart rate. After 1 month of therapy, systolic and diastolic BP were significantly decreased (p<0.05). ST and PWT were reduced, with a simultaneous increase in EDD and EDV (p<0.01). LV mass was slightly reduced, as was the M/V index. The D/Th index was increased (p<0.01). The RF contribution to EDV was increased, together with a simultaneous decrease in the AS contribution (p<0.01). The IR period was reduced (p<0.01), while vRF and vAS showed significant increases (p<0.01).After 6 months of therapy, all the above-mentioned modifications were confirmed.In conclusion, mild EH induces early modifications in LV geometry, with consequent LV diastolic abnormalities, characterized by prolonged and incomplete diastolic filling. Thus, LV wall thickness may appear increased, with a simultaneous reduction in LV diameter and volume (without any significant changes in LV mass). Antihypertensive treatment with a Ca2+ antagonist (nifedipine) induces early regression of such abnormalities with normalization of LV diastolic function.

Left ventricular diastolic function during adrenergic stress in essential hypertension: acute and chronic effects of ACE inhibition

SummaryWe studied the changes in left ventricular (LV) diastolic function induced by angiotensin-converting enzyme (ACE) inhibition at rest and during adrenergic stimulation and their relation to blood pressure (BP) variations to determine whether reductions in the renin-angiotensin system may improve diastolic function irrespective of BP reduction. Echocardiographic indices of systolic and diastolic function, plasma catecholamines as estimated by high-pressure liquid chromatography, and BP variations (Dynamap) were determined at rest and during the cold pressor test (CPT) before and 6 hours and 20 days after ACE inhibition (lisinopril), 20 mg/day by mouth in 10 subjects with uncomplicated essential hypertension. Blood Pressure was significantly reduced after both 6 hours and 20 days of therapy. The cold pressor test induced similar increases in BP in both basal conditions and after acute and chronic treatment. Catecholamine levels were unchanged by the therapy. Systolic function, evaluated by fractional shortening, ejection fraction, and systolic dV/ dt, was normal and unchanged during CPT and after treatment. Diastolic function, assessed by volume curve analysis, showed a reduced percentage contribution of rapid filling to total diastolic filling, an increase in the contribution of the atrial systole, and an increase in the isovolumetric relaxation time. During CPT these parameters deteriorated further in response to increased afterload. Lisinopril therapy induced significant increases in end-diastolic volume (p<0.005) with a progressive increase in the rapid filling dV/dt (p<0.005 at rest; p<0.001 during CPT) and a reduction in isovolumetric relaxation (p<0.001 at rest and p<0.01 during CPT). The correlation between systolic BP (afterload) and the rapid filling dV/dt, both at rest and during CPT, was modified by treatment with the ACE inhibitor, with significantly higher rapid filling dV/dt values, and with the pressure loads equal treduction of the slope and rightward shift of the correlation line). The improvement in diastolic function achieved by ACE inhibition at rest and during CPT appears unrelated to plasma catecholamines and only partly ascribable to the reduced pressure load. The tissue angiotensin II reduction might by itself improve the myocardial response to the pressure load and adrenergic stimulation.

REDUCED URINARY EXCRETION OF CALCIUM IN PREGNANCY-INDUCED HYPERTENSION: RELATIONSHIP TO RENAL PROSTAGLANDIN EXCRETION

Urinary excretion of calcium, sodium, creatinine, proteins and renal prostaglandins (PGE2, 6kPGF1α) and serum levels of calcium, sodium, creatinine and albumin were determined in 10 normotensive pregnant women throughout pregnancy and in 30 normotensive pregnant women (NTP) and 30 women with pregnancy-induced hypertension or preeclampsia (HTP) and intact kidney function in the third trimester in comparison with 13 nonpregnant control subjects (C).Urinary excretion of calcium was found to be significantly reduced in the HTP group and was correlated with PGE2 excretion (p < 0.01). A weak correlation was detectable in the NTP group, which, however, as in the HTP and C groups, showed a close correlation between urinary calcium and sodium values (p < 0.05). In the NTP group, there was a significant increase in calcium excretion, which might reasonably be regarded as related to increased renal PG activity.

Left ventricular diastolic function and responses to adrenergic stimuli in borderline arterial hypertension

Objective: To detect the existence of a possible relationship between arterial hypertension and adrenergic reactivity to pressure stimuli, and changes in left ventricular diastolic function (LVDF). Patients: Fifty-nine young subjects with borderline arterial hypertension and ten sex- and age-matched controls were investigated. After three medical examinations, the subjects were divided into hypertensive and borderline groups on the basis of the blood pressure reading at visit 3. A complete echocardiographic study was performed in 25 of the 59 subjects. Design: Blood pressure was measured in baseline conditions and during pressure stimuli (mental stress, handgrip and cold pressor tests). LVDF was evaluated primarily by means of filling velocities during diastolic phases taken from the left ventricular volume curve (obtained from a complete echocardiographic study). Results: No significant changes in blood pressure responses were observed for the borderline or hypertensive groups during the adrenergic test. The echocardiographic indices of diastolic function were statistically different for the two groups when compared with the control group. The LVDF parameters correlated significantly with systolic blood pressure and diastolic blood pressure measured at the time of the echocardiogram, but not with blood pressure measured occasionally. Conclusions: Blood pressure increases similarly during adrenergic stimuli in both the hypertensive and borderline groups. The correlation between systolic blood pressure, diastolic blood pressure and LVDF parameters may indicate a very early onset of reduced compliance of the left ventricle, even in a preclinical phase of hypertension.

Interaction between non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors in man

Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure (BP) by two possible mechanisms: reducing the formation of angiotensin II and aldosterone, and increasing the production of kinins (angiotensin-converting enzyme is also a kininase II) (Figure 1). This leads to a decreased vasoconstriction of the kinin and to a potentiation vasodepressor system with vasodilatory and antihypertensive effectsl. A rise in kinin levels stimulates an increased synthesis of vasodepressor prostaglandins (PGs), especially prostacyclin (PGI2)2. Moreover, some authors have shown an increase in PG production after captopril administration3–5. Therefore the prostaglandin system could be involved in the mechanism of action of ACE inhibitors and prostaglandin synthetase inhibitors could reduce their antihypertensive activity. In man a reduction of the antihypertensive activity of ACE inhibitors was observed when non-steroidal anti-inflammatory drugs (NSAIDs) were administered6,7.