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Biomedical subjects

A Salvetti

Publications and source records attributed to A Salvetti.

At least 73 records · Page 4Linked to original sources
PubMed1998

Utility of plasma dehydroepiandrosterone sulphate determination in adrenal incidentalomas.

To evaluate whether low DHEA-S levels are predictors of cortical origin, benignity and hormonal activity in incidentally detected adrenal masses, thirty-five patients with adrenal incidentalomas were studied. All patients were operated on and the diagnosis was histologically confirmed. Basal endocrine workup included plasma determination of cortisol before and after dexamethasone (1 mg overnight), plasma ACTH (08:00 h), 17-OH-progesterone, testosterone and potassium, standing plasma renin activity and aldosterone, supine and standing plasma noradrenaline and adrenaline. If necessary, we performed dexamethasone suppression tests at low (2 mg) and high (8 mg) doses, or the loperamide test (16 mg os) for evaluation of glucocorticoid activity and the glucagon test (1 mg i.v.) for exploring adrenal medulla function. Plasma DHEA-S was measured in all patients and the results were compared to those obtained in controls matched for age, sex and menopausal status. Suppression of DHEA-S was found in 11 out of 35 patients (31.5%). However, this hormonal finding occurred in 50% of the extracortical adrenal lesions, while in proven cortical adenomas (no. = 19) it was detected in only 5 patients (26.3%). Sensitivity, specificity, diagnostic accuracy and positive predictive value of low DHEA-S in indicating a cortical origin of the mass were 0.27, 0.0, 0.25, and 0.80. In malignancies (no. = 6) low DHEA-S levels were found in 1 out of 2 metastases and never in cortical carcinomas. Sensitivity, specificity, diagnostic accuracy and positive predictive value of low DHEA-S in indicating a benign form were 0.34, 0.83, 0.42, and 0.91. Six out of 19 patients with cortical adenomas showed signs of hypothalamic-pituitary adrenal (HPA)-axis dysfunction. Low DHEA-S levels were found in 50% of adenomas with HPA-axis abnormality and in 15.3% of adenomas without hormonal activity. Sensitivity, specificity, diagnostic accuracy, and positive predictive value of low DHEA-S levels in indicating hormonal activity of the mass were 0.50, 0.84, 0.73, and 0.60. Our data indicate that the association between low DHEA-S levels and adrenal incidentalomas is frequent. Low DHEA-S appears to be a poor predictor of hormonal activity with low sensitivity and specificity in respect of cortical origin and benignity of the mass. In conclusion, our results show that DHEA-S measurement does not offer relevant clinical information in the management of adrenal incidentalomas.

Adenoma↗
PubMed1998

Sixty adrenal masses of large dimensions: hormonal and morphologic evaluation.

OBJECTIVES: To evaluate the nature and function of adrenal masses of large dimensions (macrotumors). METHODS: Sixty consecutive patients (31 women, 29 men, age range 15 to 84 years) with adrenal masses 4.0 cm in diameter or larger (range 4.0 to 15.0 cm) underwent morphologic study by computed tomography (CT); the majority also underwent 131-I-6beta-norcholesterol (131I-NC) or 131I-MIBG scintigraphy. Basal evaluation of glucocorticoids, mineralcorticoids, and catecholamines was performed in all patients, and in 38 cases determination of androgens was also made. In addition, on the basis of various clinical suspicions, a dynamic hormonal study was performed. RESULTS: Macrotumors were benign in 78.3% of cases and included pheochromocytomas (n = 17), nonfunctioning cortical adenomas (n = 12), and cortisol-secreting tumors (n = 7, Cushing's syndrome). Malignant forms were 21.7% of the total, including pheochromocytomas (n = 3), cortical carcinomas (n = 6), and metastases (n = 4). On CT, malignant masses were larger (8.4+/-0.9 cm) than benign ones (5.7+/-0.3 cm) (P < 0.0001) and the mass size was strictly related to malignancy (P < 0.03). CT did not offer other diagnostic criteria for malignancy, except irregular margins and regional lymph node enlargement, which were more frequently (P < 0.0001) found in malignant forms. 131I-MIBG scintigraphy showed tracer uptake in all pheochromocytomas, both benign and malignant. By contrast, on 131I-NC scintigraphy, cortical malignancies never accumulated the radiotracer, whereas uptake was observed in all cases of solid cortical benign adenomas. Patients with cortical carcinomas showed plasma sex steroids above the normal range, pheochromocytomas were asymptomatic in 15% of cases, and almost half of the patients with Cushing's syndrome did not show clinical features of the disease (pre-Cushing's syndrome). CONCLUSIONS: Adrenal macrotumors frequently show endocrine activity and the medulla seems to be involved more than the cortex. Pheochromocytomas and cortisol-secreting adenomas are sometimes asymptomatic. Malignancy is often found in macromasses and, at least for the cortical forms, size of the tumor on CT, 131I-NC uptake on scintigraphy, and determination of levels of sex steroids seem to be useful criteria for predicting the nature of the mass.

Adolescent↗
PubMed1998

Endogenous digitalis-like factor and ouabain immunoreactivity in adrenalectomized patients and normal subjects after acute and prolonged salt loading.

The aim of our study was to evaluate whether adrenals are involved in the secretion of endogenous digitalis-like factor(s) with polarity similar to (or less than) that of ouabain (EDLF-1), and whether acute plasma volume expansion is a physiological releasing stimulus for this factor(s) in humans. For this purpose, we measured the concentration of this substance(s) by a human placenta radioreceptor assay (RRA) and by the Du-Pont-NEN ouabain-EIA (immunoreactive ouabain, I-Oua) in plasma C18-extracts of eight normotensives and six patients with bilateral adrenalectomy before and after acute salt loading (2 lt 0.9% NaCl/2 h). The study was repeated after 2 weeks of increased sodium intake (200 mEq/day). Under basal conditions, EDLF-1 by RRA and I-Oua were similar in adrenalectomized patients and in controls and were not significantly modified by saline infusion. After 15 days of high sodium intake, basal plasma EDLF-1 and I-Oua were not significantly different from prediet levels, both in adrenalectomized patients and controls and were likewise unaffected by saline loading. Saline infusion, by contrast, significantly (P < or = .05) suppressed hematocrit and PRA and increased ANP both in controls and in patients, either before or after prolonged high dietary sodium. Plasma aldosterone (ALD) was similarly reduced (P < .001) in controls and, as expected, was undetectable in adrenalectomized patients. Our data indicate that in adrenalectomized patients circulating levels of EDLF-1 and I-Oua are similar to those of controls and that, in both groups, acute saline loading before and after sodium repletion does not influence circulating levels of these compounds. These findings suggest that, at least in humans, adrenals are not the main source of endogenous digitalis-like factor(s) with polarity similar to (or less than) that of ouabain, and that plasma volume expansion may be not a sufficient stimulus for the release of this factor(s).

Adrenal Glands↗
PubMed1998

Effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients.

BACKGROUND: Essential hypertension is characterized by an impairment of endothelium-dependent vasodilatation. OBJECTIVE: To test whether antihypertensive treatment with the angiotensin converting enzyme inhibitor lisinopril can improve vasodilatation in response to endothelium-dependent agonists in essential hypertensive patients. DESIGN AND METHODS: We studied the effect of acute (6-8 h after dosing), prolonged (1 month) and chronic (12 months) lisinopril treatment on forearm blood flow response (strain-gauge plethysmography) induced in 10 hypertensive patients (aged 43.6 +/- 8.1 years, blood pressure 151.4 +/- 6.8/99.8 +/- 3.3 mmHg) by intrabrachial infusions of 0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml per min acetylcholine and 5, 15, and 50 ng/100 ml per min bradykinin, two endothelium-dependent vasodilators, and 1, 2, and 4 microg/100 ml per min sodium nitroprusside, an endothelium-independent vasodilator. At baseline, vascular response was compared with that of 10 normotensive subjects (aged 42.4 +/- 6.6 years, blood pressure 118.4 +/- 6.1/77.8 +/- 3.4 mmHg). RESULTS: Hypertensive patients had blunted (P < 0.01 or less) vasodilatations in response to infusions of acetylcholine (from 3.7 +/- 0.3 to 18.3 +/- 4.9 ml/100 ml per min) and bradykinin (from 3.7 +/- 0.4 to 15.8 +/- 2.6 ml/100 ml per min) compared with those of controls (from 3.6 +/- 0.3 to 25.3 +/- 5.2 ml/100 ml per min for acetylcholine and from 3.7 +/- 0.3 to 26.9 +/- 4.9 ml/100 ml per min for bradykinin) whereas the responses to infusion of sodium nitroprusside were similar (from 3.6 +/- 0.3 to 18.5 +/- 3.9 and from 3.6 +/- 0.3 to 16.4 +/- 1.8 ml/100 ml per min, respectively). Acute and prolonged lisinopril treatments significantly (P < 0.05 or less) improved vasodilatation in response to infusion of bradykinin (from 3.7 +/- 0.4 to 24.5 +/- 4.9 and from 3.7 +/- 0.3 to 22.1 +/- 4.9 ml/100 ml per min, respectively), but not in response to infusions of acetylcholine and of sodium nitroprusside. Chronic lisinopril treatment increased (P < 0.05) the response to infusions of not only bradykinin (from 3.5 +/- 0.5 to 27.6 +/- 5.3 ml/100 ml per min), but also of acetylcholine (from 3.5 +/- 0.5 to 27.8 +/- 8.0 ml/100 ml per min) and sodium nitroprusside (from 3.4 +/- 0.6 to 25.9 +/- 8.5 ml/100 ml per min). However, when the responses to infusions of acetylcholine and bradykinin were normalized with respect to that to infusion of sodium nitroprusside, only the vasodilatation in response to infusion of bradykinin was shown to have been increased by lisinopril treatment. CONCLUSIONS: Administration of lisinopril to patients with essential hypertension can selectively increase vasodilatation in response to infusion of bradykinin.

Acetylcholine↗
PubMed1998

The role of endothelium in human hypertension.

Endothelium-derived nitric oxide is not only a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell proliferation, monocyte adhesion and adhesion molecule expression. In several pathological conditions, such as human hypertension, nitric oxide availability is reduced. This alteration has been documented in the peripheral and coronary micro- and macrocirculation and in the renal circulation. The main mechanism leading to endothelial dysfunction is production of cyclooxygenase-dependent factors, including prostanoids and oxygen free radicals, which cause nitric oxide breakdown. Dysfunctional endothelium can be one of the main mechanisms causing vascular damage, in particular, atherosclerosis; hence, an important aim for antihypertensive treatment could reside not only in normalizing blood pressure values but also in reversing endothelial dysfunction. Available evidence indicates that different classes of antihypertensive compounds have different effects on endothelial dysfunction.

Antihypertensive Agents↗
PubMed1998

Endothelial function and common carotid artery wall thickening in patients with essential hypertension.

Intimal-medial thickening of the carotid wall is considered an early marker of atherosclerosis. Endothelial function is impaired in the presence of various cardiovascular risk factors that are implicated in the pathogenesis of atherosclerosis. To evaluate the relationship between vascular reactivity and carotid intimal-medial thickening, in 44 (mean+/-SD age, 45.7+/-8.8 years; range, 28 to 60 years; 31 men and 13 women) patients with essential hypertension who had never been treated and whose history of increased blood pressure was no longer than 12 months, we evaluated several parameters: intimal-medial thickening of the common carotid arteries (by B-mode ultrasound); forearm vascular response (by strain-gauge plethysmography) to intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL forearm tissue per minute), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute), an endothelium-independent vasodilator; calculated minimal forearm vascular resistances (the ratio between mean arterial pressure and maximal forearm vasodilation induced by 13 minutes of ischemia and 1 minute of exercise); and left ventricular mass index (on echocardiography profile). Carotid wall intimal-medial thickening showed a significant (P<0.001) inverse correlation with vasodilation to acetylcholine (r=-0.58) and age (r=-0.40), whereas no correlation was observed with the response to sodium nitroprusside or with minimal forearm vascular resistances, left ventricular mass index, systolic and diastolic blood pressures, and plasma cholesterol and glucose levels. Moreover, vasodilation to acetylcholine showed no correlation with minimal forearm vascular resistances or left ventricular mass index. Although comparison of different vascular "districts," such as the forearm microcirculation and carotid artery, does not allow for a conclusive interpretation, the present data indicate that in patients with essential hypertension, carotid wall thickening is associated with reduced endothelium-dependent vasodilation and suggest that endothelial dysfunction might be involved in early arterial structural alterations.

Acetylcholine↗
PubMed1998

Conventional and ambulatory measurements of blood pressure in old patients with isolated systolic hypertension: baseline observations in the Syst-Eur trial.

OBJECTIVES: To compare clinic and am measurements of blood pressure in old patients with isolated systolic hypertension and their reproducibilities. PATIENTS: In total 610 patients aged >/= 60 years with isolated systolic hypertension detected by clinic measurement were monitored during the placebo run-in phase of the Syst-Eur trial. METHODS: The time-weighted 24 h blood pressure, clock-time day and night blood pressures, the cumulative-sum-derived crest and trough blood pressures and the high and low blood pressure levels according to the square-wave model were computed. The daily alteration between the high and low spans of blood pressure was quantified using the day-night difference, the cumulative-sum-derived magnitude of circadian alteration, the Fourier amplitude and the difference between the high and low blood pressure levels of the square-wave model. RESULTS: The daytime am systolic blood pressure was, on average, 21 mmHg lower than the clinic systolic blood pressure, whereas diastolic pressure was, on average, similar with both techniques of measurement. Clinic levels of blood pressure in the 141 patients who underwent repeat measurements and the parameters describing the difference between the daily high and low spans of blood pressure were equally reproducible. However, both were less reproducible than the ambulatory blood pressure levels. The reproducibility coefficients, expressed as percentages of near maximum variation, were 49 and 50% for the clinic systolic and diastolic blood pressures, 30 and 32% for the mean 24 h systolic and diastolic blood pressures and 45-55% for the parameters describing the daily alteration between the high and low spans of blood pressure. CONCLUSION: Values of blood pressure in old patients with isolated systolic hypertension were more reproducible for ambulatory than they were for clinic measurements. Levels in patients selected because they have a high clinic blood pressure may be substantially higher with conventional than they are with daytime ambulatory measurement. The prognostic significance of this difference for the present patients is currently under investigation.

Journal Article↗
PubMed1998

Endothelial dysfunction in hypertension: fact or fancy?

Endothelium can deeply influence vascular tone and structure. The main endothelium-derived factor is nitric oxide (NO), which not only is a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell proliferation, monocyte adhesion, and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis and thrombosis. In human hypertension, endothelial dysfunction has been documented in peripheral and coronary macro- and microcirculation and in renal circulation. Impaired endothelium-dependent vasodilatation associated with essential hypertension appears to be a primary phenomenon because it can be detected in the offspring of essential hypertensive patients, shows no clear correlation with blood pressure value, and is not normalized by the mere reduction of blood pressure. The phenomenon responsible for endothelial alteration in essential hypertensive patients appears to be the activation of an alternative pathway involving cyclo-oxygenase (COX), which reduces NO availability through production of oxidative stress. This alteration in the NO pathway could be the main mechanism through which a dysfunctional endothelium may promote atherosclerosis and thrombosis in essential hypertension. Therefore, an important aim of antihypertensive therapy would be not only to normalize blood pressure values but also to reverse endothelial dysfunction by restoring NO availability. Evidence indicates that different classes of antihypertensive compounds have different effects on this alteration. Dihydropiridine calcium antagonists appear to act specifically on the NO pathway by a mechanism that is probably related to antioxidant activity.

Endothelium, Vascular↗
PubMed1997

Insulin sensitivity, vascular reactivity, and clamp-induced vasodilatation in essential hypertension.

BACKGROUND: Insulin resistance and vascular abnormalities have both been described in patients with essential hypertension. Whether these defects are associated with one another in the same individual has not been established. METHODS AND RESULTS: Whole-body insulin sensitivity (by the insulin clamp technique), forearm minimal vascular resistances, and the dose-response curve to acetylcholine, sodium-nitroprusside, and norepinephrine were measured in a group of 29 male patients with untreated essential hypertension. When the patients were divided into tertiles according to their level of insulin sensitivity, resistant and sensitive hypertensives were matched on several potential confounders of insulin action and vascular function. These subgroups showed similar minimal vascular resistances (2.5+/-0.2 versus 3.2+/-0.6 mm Hg per mL x min(-1) x dL(-1)) and superimposable responses to graded intraarterial infusions of acetylcholine, sodium-nitroprusside, and norepinephrine. No correlation was found between the vascular parameters (slope of the curve or maximal response) and insulin-mediated glucose uptake in the whole group. During the clamp, insulin sensitive patients tended to have greater increments in forearm blood flow when compared to their insulin resistant counterparts (+53+/-21 versus +9+/-7%, P=.06); in the whole group, clamp-induced vasodilatation was weakly related to insulin-mediated glucose uptake (r=.44, P<.02) as well as to the slope of the acetylcholine dose-response curve (r=.40, P<.04). Together, these two responses explained 30% (multiple r=.55, P<.01) of the variability in insulin-induced vasodilatation. CONCLUSIONS: Metabolic insulin resistance in essential hypertension is not associated with abnormalities in vascular structure, acetylcholine or nitroprusside-induced vasodilatation, or vascular adrenergic reactivity. Degree of insulin sensitivity and acetylcholine sensitivity explain a small portion of the variability of the clamp-induced vasodilatation in hypertensive patients.

Acetylcholine↗
PubMed1997

Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. SAMPLE Study Group. Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation.

BACKGROUND: In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression of organ damage over time better than clinic BP, however, is unknown. METHODS AND RESULTS: In 206 essential hypertensive subjects with left ventricular hypertrophy (LVH), we measured clinic supine BP, 24-hour ABP, and left ventricular mass index (LVMI, echocardiography) before and after 12 months of treatment with lisinopril (20 mg UID) without or with hydrochlorothiazide (12.5 or 25 mg UID). Measurements included random-zero, clinic orthostatic, and home BP. In all, 184 subjects completed the 12-month treatment period. Before treatment, clinic supine BP was 165 +/- 15/105 +/- 5 mm Hg (systolic/diastolic), 24-hour average BP was 149 +/- 16/95 +/- 11 mm Hg, and LVMI was 158 +/- 32 g/m2. At the end of treatment, they were 139 +/- 12/87 +/- 7 mm Hg, 131 +/- 12/83 +/- 10 mm Hg, and 133 +/- 26 g/m2, respectively (P < .01 for all). Before treatment, LVMI did not correlate with clinic BP, but it showed a correlation with systolic and diastolic 24-hour average BP (r = .34/.27, P < .01). The LVMI reduction was not related to the reduction in clinic BP, but it was related to the reduction in 24-hour average BP (r = .42/.38, P < .01). Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes. No substantial advantage over clinic supine BP was shown by clinic orthostatic, random-zero, and home BP. CONCLUSIONS: In hypertensive subjects with LVH, regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP. This provides the first longitudinally controlled evidence that ABP may be clinically superior to traditional BP measurements.

Adult↗
PubMed1997

Frequency of pheochromocytoma in adrenal incidentalomas and utility of the glucagon test for the diagnosis.

To investigate the frequency of pheochromocytoma in patients with incidentally discovered adrenal masses (incidentalomas) and to evaluate the sensitivity, specificity and diagnostic accuracy of the Glucagon test in comparison with resting plasma catecholamines, 89 patients with adrenal incidentalomas (age range 23-80 yr; 41 males and 48 females) were studied. Fifty-seven patients were normotensive (SBP 130+/-1.8 mmHg; DBP 80+/-0.7 mmHg, mean+/-SE) and 32 had stable hypertension (SBP 155+/-3.3 mmHg, DBP 93+/-1.4 mmHg): no patient complained of typical signs or symptoms of pheochromocytoma. Resting plasma samples for noradrenaline and adrenaline determination and, at appropriate intervals, the Glucagon test (1 mg i.v.), were performed in all subjects. Diagnosis of pheochromocytoma was made on the basis of humoral evaluations and/or surgical intervention in 6 patients (6.7%), of whom 3 hypertensives and 3 normotensives. Resting plasma catecholamines revealed 5 out of 6 patients with pheochromocytoma: in 3 cases both catecholamines were above the normal range, in 1 only adrenaline was elevated and in 1 case only noradrenaline. Similarily, the glucagon test identified 5/6 pheochromocytomas: in 3 patients the response was abnormal for both catecholamines, in 1 only for adrenaline and in 1 case only for noradrenaline. The sensitivity, specificity, and diagnostic accuracy of resting plasma catecholamines and of the glucagon test were comparable: 83.3%, 96.3%, and 95.5%, respectively. In conclusion, the frequency of pheochromocytoma in adrenal incidentalomas is not negligible, and since the diagnostic accuracy of the Glucagon test is the same of that of resting plasma catecholamines, the former does not appear to offer additional advantages in the diagnosis of incidentally discovered pheochromocytomas.

Adrenal Gland Neoplasms↗
PubMed1997

Microalbuminuria and renal haemodynamics in essential hypertension.

The present study was designed to evaluate the renal haemodynamic pattern of never-treated microalbuminuric and normoalbuminuric patients with essential hypertension. A total of 19 never-treated essential hypertensive patients with microalbuminuria were selected and, as control subjects, 24 never-treated essential hypertensive patients without microalbuminuria (determined on three 24-h urine collections) were recruited. In the two groups, we compared blood pressure values, standing plasma noradrenaline, plasma renin activity, plasma aldosterone, urinary aldosterone, lipid profile, serum glucose and uric acid, glomerular filtration rate and renal plasma flow. In comparison with normoalbuminuric patients, microalbuminuric patients showed significantly higher systolic blood pressure values (P < 0.05), higher renal vascular resistances (P < 0.05) and lower plasma renin activity values (P < 0.01). Urinary albumin excretion showed a significant positive correlation with systolic (r = 0.46, P < 0.005) and mean blood pressure (r = 0.38, P < 0.05), serum uric acid (r = 0.43, P < 0.005) and triglyceride values (r = 0.36, P < 0.005), and a significant negative correlation with plasma renin activity (r = -0.34, P < 0.05). The present data are consistent with the occurrence of renal vasoconstriction in microalbuminuric never-treated essential hypertensive patients.

Adult↗
PubMed1997

24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. Irbesartan Multicenter Investigators' Group.

OBJECTIVES: To compare 24 h ambulatory blood pressure and trough office blood pressure lowerings after 8 weeks of therapy with 75 mg irbesartan once a day, 150 mg irbesartan once a day , and 75 mg irbesartan twice a day versus placebo; and to assess safety and tolerability of irbesartan therapy. DESIGN: Multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Sixteen centers in Italy. PATIENTS: Caucasian patients (n = 215) aged > or = 18 years with seated diastolic blood pressure 95-110 mmHg and ambulatory diastolic blood pressure (ADBP) > or = 85 mmHg. PRIMARY OUTCOME: Mean 24 h ADBP after 8 weeks of irbesartan therapy. RESULTS: Mean changes (value before treatment minus value after treatment) in ADBP for placebo, 75 mg irbesartan once a day, 150 mg irbesartan once a day, and 75 mg irbesartan twice a day were -0.2, -5.4, -7.2, and -7.2 mmHg, respectively; respective changes in ambulatory systolic blood pressure were +1.6, -8.3, -10.5, and -9.7 mmHg. All irbesartan regimens reduced trough office seated diastolic blood pressure and seated systolic blood pressure after 2 and 8 weeks of treatment (all P < 0.01, versus placebo except for seated systolic blood pressure in patients in the 75 mg irbesartan once a day group). Trough: peak ratios were > or = 55% with 150 mg irbesartan once a day. Percentages of patients whose blood pressures were normalized with 150 mg irbesartan once a day (45%) and 75 mg irbesartan twice a day (47%) were greater than those with placebo (14%, P < 0.01) and with 75 mg irbesartan once a day (19%, NS, versus placebo). Adverse events with irbesartan were similar to those with placebo. CONCLUSIONS: All irbesartan regimens significantly reduced mean 24 h ADBP and ambulatory systolic blood pressure, and were well tolerated. Administration of 150 mg irbesartan once a day provided significant reduction of blood pressure for 24 h, equivalent to that obtained with the same daily dose divided into two separate administrations.

Aged↗
PubMed1997

Cutaneous vasodilation to acetylcholine in patients with essential hypertension.

Endothelium-dependent vasodilation is reduced in the forearm of patients with essential hypertension. To evaluate whether endothelium-dependent vasodilation is also reduced in the skin microcirculation of patients with essential hypertension, we evaluated the effect of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, an endothelium-independent vasodilator, on cutaneous and total forearm blood flow in normotensive subjects (n = 8) and matched patients with essential hypertension (n = 9). We infused acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml forearm tissue/min) and sodium nitroprusside (1, 2, and 4 microg/100 ml forearm tissue/min) into the brachial artery, and we measured cutaneous blood flow (laser Doppler flowmeter) and muscle blood flow (strain-gauge venous plethysmography) modifications. Both the cutaneous and muscle blood flow increases induced by acetylcholine were reduced in patients with essential hypertension as compared with normotensive controls, whereas the skin and muscle vasodilation induced by sodium nitroprusside was similar in the two groups of patients. These data confirm the impairment of endothelium-dependent vasodilation in the muscle vascular bed of patients with essential hypertension and demonstrate the presence of endothelial dysfunction in skin microcirculation.

Acetylcholine↗
PubMed1997

Gene transfer into the kidney: current status and limitations.

Gene therapy is obviously a controversial issue and a wave of suspicion has dampened the initial enthusiasm raised by this new therapeutic approach. It has now become fashionable to downplay the potential for gene therapy in most fields including kidney-related diseases. In our opinion, this is an unfair and unrealistic view of the future. In fact, gene therapy of well-selected kidney diseases will certainly become feasible, but a large data base on vectors and transfer methods both in the normal kidney and in disease models has first to be collected. Any significant progress in the biology of the vectors, in the cellular interactions of the newly introduced DNA, and in the regulation and persistency of the transgene should be rapidly translated to the kidney in relevant experimental models. Herein, we present the use and current limitations of gene transfer to the kidney and the potential therapeutic perspectives.

Animals↗
PubMed1997

Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P < .01) reduction in acetylcholine-induced vasodilation compared with baseline (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%; ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/- 36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50 micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/- 43.1%; P < .01 versus ovariectomy), which was no longer different from baseline, whereas the response to sodium nitroprusside was not affected (maximum percent increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.

Acetylcholine↗