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L Ghiadoni

Publications and source records attributed to L Ghiadoni.

50 records · Page 3Linked to original sources
PubMed1996

Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients.

BACKGROUND: Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to investigate whether this abnormality is a primary defect or a consequence of blood pressure increases. METHODS AND RESULTS: In offspring of essential hypertensive patients (n = 34) and normotensive subjects (n = 30), we evaluated forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator. Minimal forearm vascular resistances also were calculated as the ratio between mean intra-arterial pressure and maximal forearm blood flow induced by forearm ischemia and hand exercise. Vasodilation to acetylcholine was significantly (P < .01) blunted in offspring of hypertensive patients compared with offspring of normotensive subjects, whereas the responses to sodium nitroprusside and minimal forearm vascular resistances were similar. In two subgroups of 14 offspring of essential hypertensive patients but not in 10 offspring of normotensive subjects, vasodilation to acetylcholine was increased by intra-brachial L-arginine (1 mumol.100 mL-1.min-1), the substrate for nitric oxide synthesis, whereas in the other 10 and 8 offspring of essential hypertensive patients and normotensive subjects, respectively, cyclooxygenase blockade by intra-brachial indomethacin (50 micrograms.100 mL-1.min-1) was ineffective. CONCLUSIONS: Offspring of essential hypertensive patients are characterized by a reduced response to acetylcholine linked to a defect in the nitric oxide pathway, suggesting that an impairment in nitric oxide production precedes the onset of essential hypertension.

Acetylcholine↗
PubMed1996

Presence of cardiovascular structural changes in essential hypertensive patients with coronary microvascular disease and effects of long-term treatment.

In asymptomatic essential hypertensive patients with angiographically normal coronary arteries and without left ventricular hypertrophy, dipyridamole-induced ischemic-like ST segment depression may be a marker of coronary microvascular disease. In this study we evaluated, first, whether this cardiac abnormality is linked to structural or functional vascular abnormalities, and second, the effect of antihypertensive treatment by 12-month administration of the angiotensin converting enzyme (ACE) inhibitor captopril (50 mg twice a day orally). In essential hypertensives with dipypridamole echocardiography stress test (DET) (DET+, n = 8) and without (DET-, n = 8) ST segment depression greater than 0.1 mV during intravenous dipyridamole infusion (0.84 mg/kg over 10 min), we studied the forearm blood flow (FBF, venous plethysmography, mL/100) modifications induced by intrabrachial acetylcholine (Ach) (0.15, 0.45, 1.5, 4.5, 15 micrograms/100 mL/min x 5 min each), an endothelium-dependent vasodilator, and by sodium nitroprusside (SNP) (1, 2, 4 micrograms/100 mL/min x 5 min each), a smooth muscle cell relaxant compound. Minimal forearm vascular resistances (MFVR), an index of arteriolar structural changes, were also calculated. Both Ach and SNP caused greater vasodilation in DET- as compared to DET+ while MFVRs were lower in DET- compared to DET+. After treatment, both DET+ and DET- patients showed a significant and similar reduction in blood pressure and left ventricular mass index, while vasodilation to acetylcholine and sodium nitroprusside was increased only in the DET+ group. In addition, forearm minimal vascular resistances were significantly reduced only in DET+ patients, who showed disappearance of dipyridamole-induced ischemic-like ST segment depression. In conclusion, these data confirm that essential hypertensive patients with microvascular coronary disease are characterized by the presence of structural changes in the forearm vascular bed. Our results also indicate that both cardiac and forearm vascular abnormalities can be reversed by antihypertensive treatment with an ACE inhibitor.

Acetylcholine↗
PubMed1996

Menopause is associated with endothelial dysfunction in women.

To evaluate the effect of endogenous estrogens on endothelial function in humans, we examined whether menopause is associated with impairment in endothelium-dependent vasodilation in normotensive and essential hypertensive women. In 73 normotensive subjects (37 women, 36 men) and 73 hypertensive patients (36 women, 37 men), we studied endothelial function by measuring forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1,2, and 4 micrograms/100 mL per minute), an endothelium-independent vasodilator. Women younger than 45 years had normal menstrual cycles. In essential hypertensive patients, responses to acetylcholine but not to sodium nitroprusside were significantly (P < .001) reduced compared with responses in normotensive subjects. Moreover, in both groups, vasodilation to acetylcholine showed a marked negative correlation with advancing age (normotensive subjects: r = -.88, P < .001; hypertensive patients: r = -.87, P < .001). In contrast, vasodilation to sodium nitroprusside showed a less evident negative correlation with advancing age (normotensive subjects: r = -46, P < .01; hypertensive patients: r = -.48, P < .01). However, in normally menstruating normotensive women, no endothelial dysfunction was observed, and age-related impairment in endothelium-dependent vasodilation was evident only after menopause. In normally menstruating hypertensive women, aging was associated with endothelial dysfunction although the deterioration of endothelium-dependent vasodilation was less marked than that in men. In contrast, after menopause, the age-related endothelial dysfunction in hypertensive women was similar to that observed in men. Finally, no sex-related difference in the response to sodium nitroprusside was observed in either normotensive subjects or essential hypertensive patients. Age-related endothelial dysfunction is attenuated in premenopausal normotensive and hypertensive women compared with men, whereas no sex-induced difference is observed after menopause, suggesting a protective effect of endogenous estrogens on endothelial function.

Acetylcholine↗
PubMed1995

Aging and endothelial function in normotensive subjects and patients with essential hypertension.

BACKGROUND: Experimental data from normotensive and hypertensive animals indicate that aging is associated with impaired endothelium-dependent relaxations to acetylcholine, and this possibility appears to be confirmed in the human coronary artery. In the present study, we evaluated the effect of age on endothelial responsiveness in the forearm vessels of either normotensive control subjects or essential hypertensive patients. METHODS AND RESULTS: Within the normotensive or hypertensive group (n = 53 and n = 57, respectively), subjects were selected with similar blood pressure, plasma cholesterol, and glucose values, and hypercholesterolemic subjects, diabetics, and smokers were excluded. We evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 micrograms/100 mL per minute), an endothelium-independent vasodilator. Acetylcholine caused a dose-dependent vasodilation that was significantly (P < .01) lower in essential hypertensive patients than in normotensive control subjects. However, a significant negative correlation was observed between acetylcholine-induced vasodilation and patient age in both normotensive (r = -.86, P < .001) and hypertensive (r = -.85, P < .001) patients. In contrast, vasodilation to sodium nitroprusside was similar in normotensive control subjects and essential hypertensive patients with a poorer inverse correlation with patient age (normotensive control subjects, r = -.37; hypertensive patients, r = -.36) compared with acetylcholine. CONCLUSIONS: The present data indicate that there is a blunted response to acetylcholine with advancing age in both normotensive control subjects and essential hypertensive patients, suggesting that aging is associated with reduced endothelium-dependent vasodilation in humans.

Acetylcholine↗
PubMed1995

Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients.

Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum UCE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 microgm x ml(-1)), and by 12 hours the compound had almost disappeared (67 ng x ml(-1)). Derived t1/2 was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1) x min(-1) x ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 24 hours) pg x ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg; placebo 147/100 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.

Absorption↗
PubMed1995

Lack of correlation between microalbuminuria and endothelial function in essential hypertensive patients.

OBJECTIVE: To evaluate whether microalbuminuria, defined as urinary albumin excretion between 30 and 300 mg/24 h, is associated with endothelial dysfunction in essential hypertensive patients. DESIGN: We correlated urinary albumin excretion with vasodilatation in response to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) agonists in the forearm vascular bed in essential hypertensive patients with (n = 13) and without (n = 23) microalbuminuria and matched normotensive controls (n = 21). METHOD: We studied forearm vascular responses (strain-gauge plethysmography) to intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5 and 15 ng/100 ml forearm tissue/min) and of sodium nitroprusside (1, 2, 4ng/100 ml forearm tissue per min). Minimal forearm vascular resistances (the ratio between mean arterial pressure and maximal forearm vasodilation induced by 13 min of ischaemia + 1 min of exercise) were also evaluated. RESULTS: Responses to acetylcholine, but not to sodium nitroprusside, were significantly blunted and minimal forearm vascular resistances were increased in hypertensive patients compared with controls. However, no correlation was found between urinary albumin excretion and vasodilatation in response to acetylcholine or to sodium nitroprusside or between urinary albumin excretion and minimal forearm vascular resistances. CONCLUSIONS: In hypertensive patients, increased urinary albumin excretion is associated neither with functional nor with structural dysfunction in the forearm vasculature.

Acetylcholine↗
PubMed1995

[Endothelial function and arterial hypertension].

In normotensive humans, the endothelium modulates vascular tone mainly by the production of nitric oxide. In human essential hypertension the basal release of nitric oxide is reduced and forearm vasodilation to the endothelium-dependent agonists acetylcholine or bradykinin is blunted. Defective basal release of nitric oxide seems to be secondary to blood pressure increase while impaired agonist-evoked endothelium-dependent vasodilation is probably a primary phenomenon. This latter endothelial dysfunction seems to be caused by the simultaneous presence of an alteration in the L-arginine-nitric oxide pathway and the production of constrictor prostanoids. Defective nitric oxide production is already detectable in normotensive offspring of hypertensive patients and young essential hypertensives. In contrast, vasoconstrictor prostanoid production seems to be associated with aging. In essential hypertensive patients, although only scanty data are available, chronic effective pharmacological treatment seems to restore impaired basal production of nitric oxide but does not improve vascular response to endothelial agonists.

Aging↗
PubMed1994

Effect of potassium on vasodilation to acetylcholine in essential hypertension.

Patients with essential hypertension show impaired endothelium-dependent vasodilation induced by acetylcholine. Because dietary potassium supplementation increases endothelium-dependent relaxations to acetylcholine in hypertensive rats, we designed the present study to investigate whether potassium increases endothelium-dependent vasodilation in essential hypertensive patients. Therefore, in patients with essential hypertension (n = 13) and in normotensive control subjects (n = 13) we evaluated the effect of intrabrachial potassium chloride (0.2 mmol/min) on forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL forearm tissue per minute). In both groups of patients, potassium chloride infusion augmented local plasma potassium concentrations. Furthermore, in essential hypertensive patients but not in normotensive subjects it increased the vasodilating effect of the first three infusion rates of acetylcholine. In contrast, in seven adjunctive essential hypertensive patients, potassium chloride did not alter intrabrachial sodium nitroprusside-induced forearm vasodilation (1, 2, and 4 micrograms/100 mL forearm tissue per minute). Finally, to evaluate the role of nitric oxide on potassium-dependent facilitation of acetylcholine-induced vasodilation in essential hypertension, we studied the effect of intrabrachial NG-monomethyl L-arginine (100 micrograms/100 mL per minute) in another group of seven hypertensive patients. Vasodilation to acetylcholine was again increased by potassium chloride; NG-monomethyl L-arginine slightly blunted the vasorelaxing effect of acetylcholine but abolished the potentiating effect of potassium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMedDate not supplied

[Chronic inflammation and endothelial dysfunction: analysis of a cohort of patients with SLE and UCTD].

OBJECTIVE: Cardiovascular complications, mainly caused by an accelerated atherosclerosis, are one of the leading causes of death and disability in patients with systemic autoimmune diseases. Endothelial dysfunction is considered the earliest and reversible step of atherogenesis. Aim of the present study is to investigate endothelial function (EF) in patients with systemic lupus erythematosus (SLE), undifferentiated connective tissue diseases (UCTD) and correlate the results with clinical and laboratory variables. METHODS: EF was assessed on the peripheral microcirculation by the perfused forearm technique that can estimate both endothelium- dependent and endothelium- independent vasodilatation. The same evaluation has been repeated in two patients after the administration of 20 mg of 6-metilprednisolone. RESULTS: Twenty-three female patients with SLE or UCTD, with a follow up of at least 1 year have been studied and compared with 8 healthy controls matched for epidemiological variables and traditional risk factors for cardiovascular disease. A significant reduction both in endothelium dependent than endothelium independent vasodilatation was observed in both patients groups compared with controls. In addition, UCTD patients demonstrated a significant reduction in the nitric oxide pathway compared with controls and SLE patients. Finally, steroid administration induced an improvement of vascular reactivity. CONCLUSIONS: Despite the well documented side effects of chronic corticosteroid therapy, our data might suggest a role for antinflammatory and immunosuppressive therapy in the prevention of premature atherosclerosis in patients with systemic autoimmune diseases.

Adult↗
PubMedDate not supplied

Prediction and consistency of blood pressure salt-sensitivity as assessed by a rapid volume expansion and contraction protocol. Salt-Sensitivity Study Group of the Italian Society of Hypertension.

BACKGROUND: This multicenter trial in essential hypertensive patients (n=94) is aimed i) to evaluate the distribution of blood pressure salt-sensitivity by a rapid volume expansion/contraction protocol over three days; ii) to investigate the within-patient reproducibility and to identify predictors of the response to the test; iii) to compare this response with the response to dietary NaCl restriction. METHODS: The study design included: 1) screening for salt-sensitivity by the rapid test; 2) a controlled trial of dietary salt restriction; 3) repetition of the rapid test in a subgroup of patients. RESULTS: The mean BP response to the rapid test fitted a Gaussian curve. In multivariate regression analysis, controlling for the effect of potential confounders, the blood pressure increment during the intravenous saline infusion was the best independent predictor of the response to the test (r=0.713) with minor contributions by the 24-h urinary sodium excretion before the test and by baseline fasting serum insulin. These three variables together explained 61% of the overall variability of the response. The Spearman rank correlation coefficient between the BP response to the rapid test and the response to the dietary protocol was 0.21, p=0.05. Upon repetition of the rapid test, the correlation coefficient between the responses observed on the two occasions was 0.60 (n=19, p<0.01); there were no patients misclassified across the extreme tertiles of the distribution of salt-sensitivity. CONCLUSION: We conclude that the rapid test reproducibly identified patients in the upper and lower parts of the distribution of salt sensitivity. The analysis of possible predictors of the response to the test suggested that the evaluation of the blood pressure response to saline infusion, upon careful standardization of dietary NaCl intake, may represent an alternative to the completion of the whole test for the screening of the salt-sensitivity.

Adult↗
PubMedDate not supplied

Endothelial dysfunction in hypertension.

Endothelium can deeply influence vascular tone and structure. The main endothelium derived factor is nitric oxide, which is not only a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell migration and 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 vasodilation associated with essential hypertension seems to be a primary phenomenon, since 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 seems to be the activation of an alternative pathway involving cyclooxygenase 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 could be a promoter of atherosclerosis and thrombosis in essential hypertension.

Endothelium, Vascular↗
PubMedDate not supplied

Endothelial function in hypertension.

Endothelial dysfunction has been documented both in the forearm and coronary beds of essential hypertensive patients. Impairment in the tonic release of nitric oxide (NO) is secondary to hypertension, while the alteration in agonist-induced endothelium-dependent vasodilation seems to be a primary defect caused both by an alteration of the L-arginine-NO pathway and the production of cyclooxygenase-dependent EDCFs, such as prostanoids or superoxide anions. These latter substances curtail endothelium-dependent vasodilation mainly by inactivating NO production. Although experimental data clearly indicate that the L-arginine-NO pathway participates in the regulation of renal hemodynamics and renal excretory function under basal and stimulated conditions, data in humans are scanty and confounded by methodological approaches. A posteriori interpretation of data obtained with intrarenal infusion of acetylcholine in kidney donors suggests that endothelium dependent vasodilation in the kidney is impaired by aging, a phenomenon well documented in the forearm and coronary circulation. Systemic infusion of L-arginine induced renal vasodilation and natriuresis in normotensive subjects, an effect which seems to be mediated mainly by intrarenal NO production. Moreover the few available data suggest that both renal vasodilation and renal production of NO in response to L-arginine are blunted in patients with essential hypertension and that superoxide anions, may be, at least partially, responsible for this alteration of the L-arginine-NO pathway. In conclusion, endothelial dysfunction has been well documented in the forearm and coronary circulation of patients with essential hypertension. Available data suggest that endothelial, dysfunction is also detectable in the kidney and that a common mechanism, probably superoxide anions, can account for this abnormality.

Arginine↗