Maria Catalano

Basal nitric oxide production is not reduced in patients with noninsulin-dependent diabetes mellitus

Vascular disease is the leading cause of morbidity, disability and death in patients with noninsulin-dependent diabetes mellitus. Abnormalities in endothelium-derived nitric oxide (NO) have been demonstrated to be involved in the pathogenesis of vascular disease. By measuring hemodynamic responses to a NO synthase agonist or antagonist, previous studies have shown the presence of NO deficiency in patients with noninsulin-dependent diabetes mellitus, a method of assessing bioactive NO formation. However, direct biochemical evidence that this is the case, has not been produced. In vivo NO is metabolized into nitrate, an end breakdown product of NO, which can be used as an index of endogenous NO formation. To investigate further whether decreased basal synthesis of NO may be a major cause of endothelium-mediated vascular dysfunction in patients with noninsulin-dependent diabetes mellitus, the plasma nitrite/nitrate levels of 15 patients were examined and compared with 13 normal controls. The results showed that in basal conditions plasma nitrite/nitrate levels were not reduced in diabetic patients compared with normal controls (37.3 ± 14.7 versus 29.4 ± 8.6 μmol/l). It was concluded that in noninsulin-dependent diabetes mellitus patients, endothelium-derived basal NO formation is not impaired. This study, taken with previous observations, suggests that factors other than diminished basal NO production, such as reduced bioavailability of NO probably due to the augmented production of superoxide anion with subsequently increased inactivation of NO, contribute to the high incidence of vascular disease in patients with noninsulin-dependent diabetes mellitus.

Captopril for the Treatment of Patients with Hypertension and Peripheral Vascular Disease

Many epidemiological studies have shown up the frequent association of ar terial hypertension (HT) with atherosclerosis of different localizations. How ever, many of the drugs used to treat HT are contraindicated in patients with peripheral vascular disease (PVD), because they cause unfavorable metabolic changes or vasoconstriction. The aim of the present study was to assess the effect of a proven hypotensive drug, captopril, on the peripheral circulation. The drug appeared to be effec tive in improving blood flow to lower limbs, prolonging the pain. Free interval and increasing the angle/arm arteral pressure index.

Energetics of walking in patients with peripheral arterial disease: a proposed functional evaluation protocol.

The energy cost of walking (at 3.2 km x h(-1)) per unit distance (J x kg(-1) x m(-1)) at gradients of 0%, +7%, and +12% and during a progressive test (2% increase in gradient every 2 min), as well as the overall (aerobic plus anaerobic) net cumulative energy consumption and the corresponding maximal exercise duration were assessed in 19 patients with peripheral arterial disease (PAD) and in 13 moderately active control subjects. With a 0% gradient, the energy cost of walking was approximately 40% greater in patients with PAD than in controls (2.93+/-0.52 and 2.13+/-0.33 J x kg(-1) x m(-1) respectively; P <0.01). In contrast, at gradients of +7% and +12%, the energy cost of walking was similar in the two groups (+7%: PAD, 4.15+/-0.74 J x kg(-1) x m(-1); controls, 4.18+/-0.54 J x kg(-1) x m(-1); +12%: PAD, 5.59+/-1.03 J x kg(-1) x m(-1); controls, 5.64+/-0.75 J x kg(-1) x m(-1)). In patients with PAD, maximal exercise duration with gradients of 0%, +7% and +12% was 449+/-254, 322+/-200 and 229+/-150 s respectively, whereas the net cumulative energy consumption at fatigue was almost constant at approximately 1100 J x kg(-1) for all gradients. The greater energy cost of walking in PAD patients compared with controls in level, but not uphill, walking is interpreted as being mainly the consequence of an altered mechanical locomotory pattern, and not of lower metabolic efficiency. For a wide range of loads, net cumulative energy consumption appears to be independent of maximal exercise duration, a finding that provides a practical criterion for assessing the degree of functional impairment of patients with PAD on metabolic grounds.

Plasma β-Thromboglobulin Levels and Claudication Degrees in Patients with Peripheral Vascular Disease

In 30 patients with varying degrees of claudication and 40 normal subjects, plasma levels of β-thromboglobulin were determined. These were significantly higher (p < 0.01) in the patients than in age-matched controls; in the control group the β-thromboglobulin values resulted slightly higher in older subjects. No correlation was found between β-thromboglobulin and the severity of the vascular disease, assessed on the basis of the pain-free interval on the treadmill.

Lipid Profile during Antihypertensive Treatment

SummarySome antihypertensive drugs adversely affect the plasma lipid profile, and this has to be taken into account when choosing treatment for hypertension because it may offset the beneficial blood pressure-lowering effect of these agents. In this study, the long term effects of verapamil sustained release (SR) 240mg daily and enalapril 20mg daily on plasma lipid levels were investigated in 931 patients with mild to moderate hypertension. Patients whose blood pressure was not effectively lowered after at least 1 month of monotherapy had either enalapril 20mg once daily added to their verapamil treatment or hydrochlorothiazide 12.5mg once daily added to their enalapril treatment. Blood pressure and lipid profile were assessed before and after 6 months of treatment.Of 864 evaluable patients, 563 patients (65.1%) were successfully treated with monotherapy and 220 patients (25.5%) required combination therapy. A total of 81 patients withdrew from the trial. Systolic and diastolic blood pressure were significantly reduced by treatment with either verapamil or enalapril, and heart rate was reduced slightly, but significantly, by both treatments.Total cholesterol, triglycerides and low density lipoprotein were significantly reduced by both treatments. High density lipoprotein levels were significantly increased in verapamil recipients, but not in enalapril recipients. Adverse effects occurred in 37 (3.9%) patients receiving verapamil SR and 25 (2.7%) patients receiving enalapril.In conclusion, long term treatment with the antihypertensive agents verapamil and enalapril, alone or in combination regimens, significantly improved the plasma lipid profile. Verapamil SR had the most beneficial effect on plasma lipid levels.

Effects of treatment with verapamil SR and captopril on the lipid profile of hypertensive patients

SummaryThe potential beneficial effects of antihypertensive drugs on cardiovascular morbidity and mortality may be compromised by their adverse effects on serum lipid levels. In our study we compared verapamil and captopril and evaluated their effects on blood pressure and on serum lipid and lipoprotein levels, with particular attention to lipoprotein(a) [Lp(a)].20 hypertensive patients were treated with sustained release verapamil 240mg once daily or captopril 25mg twice daily for 3 months in a double-blind randomised study. Diastolic blood pressure was reduced from 100 ± 3mm Hg to 87 ± 6mm Hg (p < 0.01) and from 100 ± 5mm Hg to 92 ± 7mm Hg (p < 0.05) in the verapamil and captopril groups, respectively. Small but significant changes in serum lipid levels were noted: total cholesterol was reduced from 6 to 5.8 mmol/L (verapamil) and from 6.1 to 5.9 mmol/L (captopril); low density lipoprotein (LDL) cholesterol was reduced from 4 to 3.8 mmol/L (verapamil) and from 4.2 to 3.9 mmol/L (captopril); apolipoprotein C-III was reduced from 0.3 ± 0.07 to 0.2 ± 0.06 mmol/L (9.7 ± 2.5 to 9.2 ± 2.3 mg/dl) [verapamil] and from 0.2 ± 0.1 to 0.2 ± 0.09 mmol/L (9.1 ± 3.7 to 8.3 ±3.4 mg/dl) [captopril]; apolipoprotein A-II increased only with verapamil (p < 0.02). Lp(a) levels showed only minor changes in individual patients.In conclusion, in our study verapamil and captopril were effective antihypertensive agents and did not adversely effect the lipid profile.

Radial artery compliance in patients with peripheral vascular disease.

Compliance in largely central arteries of patients with peripheral vascular disease (PVD) has been reported to be reduced. However, the arterial tree is an inhomogeneous system, and there remains uncertainty about whether the peripheral arteries (e.g. the medium-sized muscular radial artery) undergo a similar change to the central arteries. The aim of this study was to investigate the radial artery elasticity in 19 patients with PVD compared with 18 normal subjects of comparable age and sex. Using a noninvasive high-resolution echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured the radial artery compliance by determining the diameter–pressure, compliance–pressure and distensibility–pressure curves. The results showed that the diameter of the radial artery was similar in the two groups, but that the compliance and distensibility were not further reduced in patients with PVD than in the normal controls at 100 mmHg and for a common blood pressure range. The present studies demonstrate that in patients with PVD the radial arterial compliance is not reduced, which indicates that the change in arterial elasticity is not identical. The potential mechanisms involved in this change in radial artery compliance are discussed.

Microcirculation and hemorheology in NIDDM patients.

The authors studied 10 patients with non-insulin-dependent diabetes mellitus and 5 controls matched for age, sex, blood lipids, and smoking habit. The two groups were also comparable for hemorheologic characteristics as evaluated by viscosimetry on whole blood, plasma and serum, erythrocyte filtration and aggregation. The microcirculation was studied in the subjects of both groups by microalbuminuria determination, retinal fluorangiography, and capillaroscopic examination of the bulbar conjunctive and nail folds. None of the patients presented microalbuminuria values higher than the upper limit of normal (20mg/24h). Fluorangiographic alterations were observed in 4 patients, and all 10 pre sented capillaroscopic alterations at the bulbar conjunctiva (microaneurysms, erythrocyte aggregates) and nail folds (more frequently of the fingers than toes). Similar alterations were detected in controls. Thus these abnormalities seem independent of hemorheologic values.

SKIN BLOOD FLOW DURING VASOCONSTRICTIVE AND VASODILATIVE STIMULI IN ESSENTIAL HYPERTENSION PATIENTS : A LASER DOPPLER FLOWMETRY STUDY

In order to compare the extent of the elicited vasoconstrictive and vasodilative response at the microcirculatory level in essential hypertension (EH), we measured the skin blood flow by means of a laser Doppler flowmeter (LDF). Thirty-four mild-to-moderate EH patients were enrolled. Twenty-two sex- and age-matched healthy subjects were selected as a control group. The LDF measurements were carried out with the probe over the fingertip of the distal phalanx at baseline conditions (Rest flow, RF), after an ischaemic test (post-ischaemic peak flow) and during an arithmetic stress test (AT). The flow was expressed in arbitrary units. The data were processed using the Perisoft computer program. The relative flows after the ischaemic test (Rel F1) and during the AT (Rel F2) were expressed as a percentage of the previous RF values (RF1 and RF2, respectively). During the AT, the lag time was calculated (in seconds). As compared to the control subjects, RF was significantly lower in the EH group (p < 0.01). During the AT, the EH patients showed a statistically lower mean Rel F2 decrease compared to the control subjects (p < 0.01). No statistically significant difference occurred in the Rel F1 and lag time. These data suggest that the vasoconstrictive capacity of the precapillary vessels is impaired in patients with hypertension.

A multicenter study of doxazosin in the treatment of patients with mild or moderate essential hypertension and concomitant intermittent claudication

This study assessed the efficacy and safety of once-daily doxazosin in the treatment of patients (n = 19) with mild or moderate essential hypertension (sitting diastolic blood pressure [DBP] 95 to 114 mm Hg) and concomitant intermittent claudication (Doppler ankle/arm ratio of less than 0.80 and walking tolerance of less than 700 m on the treadmill). After 14 weeks of treatment with doxazosin, a significant (p less than 0.05) reduction in systolic blood pressure and DBP was observed. Mean blood pressures were reduced from 170/100 mm Hg at baseline to 161/93 mm Hg at the end of treatment. Minor changes in heart rate occurred, which with continued treatment were not statistically significant from baseline. In 12 of 16 (75.0%) efficacy-evaluable patients blood pressure was normalized (DBP to less than or equal to 90 mm Hg with an greater than or equal to 5 mm Hg reduction from baseline) with a mean daily dose of 7.6 mg/day. Doxazosin improved the hypertension severity category in 13 of 16 (81.3%) patients. The blood pressure ratios between both the thighs and arms and ankles and arms showed no statistically significant changes after treatment with doxazosin. Thigh blood flow at rest and the reactive hyperemia after 3 minutes of arterial occlusion did not change statistically. There was a tendency for pain-free distance to improve. Laboratory data were not significantly changed after treatment with doxazosin. Of the 19 patients studied, 5 reported mild or moderate side effects that were either tolerated or disappeared with continued treatment. No patient had therapy withdrawn and no patient required a dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)