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Biomedical subjects

Antonio Salvetti

Publications and source records attributed to Antonio Salvetti.

45 records · Page 3Linked to original sources
PubMed2002

Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopril: a multicentre study.

OBJECTIVE: To compare the effect on antihypertensive efficacy produced by the addition of indomethacin to the angiotensin II (Ang II) antagonist, valsartan, or to the angiotensin-converting enzyme inhibitor, lisinopril, in hypertensive patients with chronic osteoarthritis. SUBJECTS AND METHODS: One hundred and twenty-eight patients (52 men and 76 women) aged 25-82 years (mean age 55.7 years), with diastolic blood pressure (DBP) > 100 mmHg at the end of a 2-week placebo washout period were allocated randomly to groups to receive valsartan (80-160 mg once daily) or lisinopril (10-20 mg once daily). At the end of 10 weeks of treatment, patients with DBP < 90 mmHg, while continuing to receive valsartan or lisinopril treatment, were allocated randomly to groups to receive either indomethacin (50 mg three times a day) or the corresponding placebo for 2 weeks, with a 1-week washout period between the two treatments, according to a double-blind, crossover design. After the initial washout period, patients were examined at the end of the 4th, 8th and 10th weeks of randomized treatment with valsartan and lisinopril, at the end of the first crossover period and then at the beginning and at the end of the second crossover period. At each visit, sitting and standing blood pressure were measured by standard mercury sphygmomanometer. RESULTS: The addition of indomethacin blunted the blood pressure-decreasing effect of both antihypertensive drugs. Although indomethacin produced greater increases in both systolic and DBP values in the lisinopril-treated patients (5.45/3.22 mmHg) than in the valsartan-treated ones (2.12/1.87 mmHg), no significant difference between the two drugs was found. CONCLUSIONS: From a theoretical standpoint, these findings suggest that prostaglandins may play a part in the antihypertensive action of Ang II antagonists. From a practical standpoint, hypertensive patients treated with valsartan or with lisinopril should be monitored to detect changes in blood pressure control while receiving indomethacin.

Adult↗
PubMed2002

Primary aldosteronism in normokalemic patients with adrenal incidentalomas.

OBJECTIVE: Since primary aldosteronism has been reported in asymptomatic incidental adrenal masses (adrenal incidentalomas, AI), the aim of our study was to detect primary aldosteronism in normokalemic patients with AI and to verify whether a raised plasma aldosterone (ALD)/plasma renin activity (PRA) ratio may be useful for diagnosis. DESIGN: One-hundred and twenty-five normokalemic patients with solid AI (90 hypertensives and 35 normotensives) and 82 essential hypertensives (EH) were studied. Upright ALD and PRA determination was performed in all cases while patients with abnormal ALD/PRA ratios were submitted to confirmatory tests (saline infusion and captopril tests) for diagnosis of primary aldosteronism. METHODS: ALD and PRA were measured by specific radioimmunoassays. RESULTS: PRA values in AI hypertensives (1.05+/-0.13 ng/ml/h) were lower than in AI normotensives (1.14+/-0.14 ng/ml/h, P<0.05) and in EH (1.68+/-0.15 ng/ml/h, P<0.0001). The ALD/PRA ratio in AI hypertensives (46.4+/-5.1) was higher than in AI normotensives (30.7+/-5.8, P<0.03) and in EH (33.2+/-3.5). Four patients with EH and 2 AI normotensive patients had elevated ALD/PRA ratios but normal responses to the suppressive tests, thus excluding diagnosis of primary aldosteronism. Eight patients with AI and hypertension had a high ALD/PRA ratio, and 7 of these were further studied: in 5 patients diagnosis of primary aldosteronism was well-established by dynamic tests, adrenal vein sampling or by surgery. CONCLUSIONS: Primary aldosteronism in normokalemic patients with incidentally discovered adrenal masses was detected in 4 of all cases and in at least 5.5% of those with hypertension. Consequently, these patients, particularly if hypertensive, need to be routinely studied to exclude this hormonal disease. Evaluation of the ALD/PRA ratio seems to be a simple and reliable test for diagnosis.

Adolescent↗
PubMed2002

Effects of antihypertensive drugs on endothelial dysfunction: clinical implications.

Essential hypertension is associated with endothelial dysfunction, which is caused mainly by the production of oxygen-free radicals that can destroy nitric oxide (NO), and impair its beneficial and protective effects on the vessel wall. In prospective studies, endothelial dysfunction is associated with increased incidence of cardiovascular events. Antihypertensive drugs show contrasting effects in terms of improvement or restoration of endothelial function. Little evidence is available with beta-blockers. Whereas treatment with atenolol has a negative effect in peripheral subcutaneous and muscle microcirculation, insufficient evidence is available to establish whether new compounds such as nebivolol, which activates the L-Arginine--NO pathway, and carvedilol, which has strong antioxidant activity, can improve endothelial function in patients with hypertension. Calcium channel antagonists, particularly the dihydropyridines, can reverse impaired endothelium-dependent vasodilation in different vascular districts, including the subcutaneous, epicardial, renal and forearm circulation. However, conflicting results are found in the brachial artery. In the forearm circulation, nifedipine and lacidipine can improve endothelial dysfunction by restoring NO availability through a mechanism probably related to an antioxidant effect. ACE inhibitors, on the other hand, seem to improve endothelial function in subcutaneous, epicardial, brachial and renal circulation, whereas they are ineffective in potentiating the blunted response to acetylcholine in the forearm of patients with essential hypertension. They can also selectively improve endothelium-dependent vasodilation to bradykinin, an effect not mediated by restoring NO availability but probably related to hyperpolarisation. Recent evidence suggests angiotensin II AT(1)-receptor antagonists can restore endothelium-dependent vasodilation to acetylcholine in subcutaneous microcirculation but not in that of the forearm muscle. Evidence concerning the effect of these drugs on the brachial artery in patients with atherosclerosis is positive. However, treatment with an AT(1)-receptor antagonist can improve basal NO release and decrease the vasoconstrictor effect of endogenous endothelin-1. In conclusion, despite the considerable evidence that impaired endothelium-dependent vasodilation can be improved by appropriate antihypertensive treatment, no clinical data exist demonstrating that the reversal of endothelial dysfunction is associated with a reduction in cardiovascular events. In the near future, large scale clinical trials are required to demonstrate that treatment of endothelial dysfunction can lead to better prognosis in patients with essential hypertension.

Animals↗
PubMed2002

Endothelial function in hypertension: role of gender.

Endothelium plays an important role in the modulation of vascular tone and structure mainly through the production of nitric oxide (NO), which causes local vasodilation and counteracts processes leading to atherothrombosis. A dysfunctioning endothelium, characterized by reduced NO availability owing to impairment of the L-arginine-NO pathway and, above all, to production of oxygen free radicals, can impair local vasomotion and promote the development of atherosclerosis and of atherothrombotic vascular events. Aging is associated with endothelial dysfunction both in normotensive subjects and in hypertensive patients, and hypertension seems to induce earlier onset of those mechanisms (i.e. impairment of the L-arginine-NO pathway and oxidative stress) that cause age-related endothelial dysfunction. Premenopausal normotensive women are protected against the deleterious effect of aging on endothelial function, and age-related impairment of endothelial function is attenuated in premenopausal hypertensive women. This protective effect on endothelial function seems to be mediated by endogenous estrogen, which preserves NO availability by activating the L-arginine-NO pathway in normotensive women and, again, by activating this pathway but above all by inhibiting oxidative stress in hypertensive women. Thus, the protective effect of endogenous estrogen on endothelial function could be a plausible mechanism contributing to the lower cardiovascular risk of premenopausal women. Finally, whether endogenous androgen can impair endothelial function is still an unsolved issue since data concerning the effect of testosterone on endothelial function are scanty and contradictory.

Animals↗
PubMed2001

Renal function and intensive lowering of blood pressure in hypertensive participants of the hypertension optimal treatment (HOT) study.

This article reports further analyses of the Hypertension Optimal Treatment (HOT) Study data with the aim to describe (1) the value of baseline serum creatinine and its clearance (estimated by Cockroft and Gault formula) as predictors of cardiovascular events, (2) the effects of intensive lowering of BP on cardiovascular events and renal function in patients with reduced renal function, and (3) the effects on cardiovascular events of adding acetylsalicylic acid to antihypertensive therapy in patients with reduced renal function. The results show that (1) baseline elevation in serum creatinine and a reduction in estimated creatinine clearance are powerful predictors of cardiovascular events and death. (2) Reduced renal function at baseline did not preclude the desired control of BP. In contrast to patients with normal renal function, the incidence of major cardiovascular events did not differ in the three groups of patients with mild renal insufficiency randomized to different diastolic BP targets. No significant changes in serum creatinine were seen at the end of the 3.8-yr treatment period in the great majority of patients. However, there was a small group of patients (0.58% of the total study population) whose renal function deteriorated (increase > or =30% over baseline and final serum creatinine concentration > or =2 mg/dl) despite satisfactory reduction of diastolic BP. (3) The results of this reanalysis of the HOT Study suggest though do not prove that the association of acetylsalicylic acid with intensive antihypertensive therapy offers additional benefit in hypertensive patients with reduced renal function.

Aged↗
PubMedDate not supplied

Cardiovascular parameter changes in patients with erectile dysfunction using pde-5 inhibitors: a study with sildenafil and vardenafil.

Sildenafil is the most prescribed oral agent for patients with erectile dysfunction (ED). Vardenafil is a new phosphodiesterase type 5 (Pde-5) inhibitor that was approved by the US Food and Drug Administration last year to treat patients with ED of various causes. Both of these Pde-5 inhibitors have vasodilating properties and effects on blood pressure (BP), and like nitrates, they work through the nitric oxide cyclic guanosine monophosphate pathway. The aim of this study was to investigate the influence of these Pde-5 inhibitors on BP and heart rate (HR) in normotensive men with ED by a crossover comparison. Thirty-five patients with ED were enrolled to evaluate and compare the effect of sildenafil (50 mg) and vardenafil (10 mg) on BP and HR. At the screening (baseline [B]) visit, sitting systolic blood pressure (B-SBP), diastolic blood pressure (B-DBP), and HR were measured. We performed a multiple administration for both drugs and, therefore, multiple measurements of BP and HR changes, 3 doses a week, on alternate days, late in the afternoon, and on an empty stomach. B-SBP, B-DBP, and HR were recorded before each 50-mg sildenafil dosing and after 30, 60, 120, and 240 minutes. Data were averaged over the 4 time points and compared with the baseline values obtained before each dosing. After a 3-week wash-out period, patients were crossed over to vardenafil (10 mg) with the same study design. After administration of both drugs, we observed a statistically significant decrease of BP and an increase of HR. On average, sildenafil caused a decrease of SBP ranging from 5.1 +/- 3.9 mm Hg during the first dosing to 4.7 +/- 4.2 mm Hg during the third dosing, DBP ranged from 4.4 +/- 4.9 to 4 +/- 4.1 mm Hg, and HR increased 1.8 +/- 2.0 bpm (first dose) and 1.2 +/- 0.9 bpm (third dose). With vardenafil, we recorded a greater variation for SBP and DBP. SBP decreased from 8.02 +/- 8.0 mm Hg during the first dosing to 5.4 +/- 5.5 mm Hg during the third dosing, whereas DBP decreased from 6.6 +/- 7.2 to 5.0 +/- 5.3 mm Hg, respectively. Recorded HR showed an increase of 3.1 +/- 3.2 bpm (first dose) and 2.4 +/- 2.3 bpm (third dose). After the first vardenafil administration, we recorded fainting episodes in 3 patients because of a decrease in BP greater than 20 mm Hg. Two of the patients were in therapy with doxazosin for benign prostatic hyperplasia (BPH). Cardiovascular response was not significantly different after the first dose between the 2 treatments. Vardenafil demonstrated clinically significant differences (fainting) with respect to sildenafil only during the first doses. We suggest that before starting therapies with Pde-5 inhibitors, particularly with the newer ones, that baseline cardiovascular parameters are measured and monitored, especially during the first dose, because of the presence of a "first dose effect." Moreover, it is necessary to pay particular attention to those patients in treatment with other drugs that could have a synergistic hypotensive effect as a result of vasodilation potentiation.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

Efficacy and tolerability of manidipine in the treatment of hypertension in patients with non-diabetic chronic kidney disease without glomerular disease. Prospective, randomized, double-blind study of parallel groups in comparison with enalapril.

BACKGROUND: Calcium channel blockers (CCBs) are effective blood pressure lowering agents, giving rise to a prevalent dilation of the afferent arteriole. Manidipine, a long-lasting dihydropyridine CCB, demonstrates its action not only on the afferent arteriole, but also on the efferent one. This suggests theoretically a renoprotective effect in patients with chronic kidney diseases (CKD). METHODS: This was a multicenter, prospective, randomized, double-blind, parallel group study, to evaluate the efficacy and tolerability of manidipine (M; 10-20 mg/day), in comparison with enalapril (E; 10-20 mg/day) in the treatment of hypertension in 136 patients with CKD secondary to primary renoparenchymal disease. Changes in blood pressure values from baseline were considered as the primary outcome of the study. Proteinuria changes and the rate of renal function decline were also evaluated. RESULTS: During a 48-week follow-up, mean SBP decreased from 155+/-11.7 to 138.7+/-13.9 mmHg in M and from 157.3 +/-11.8 to 134.2+/-13.9 mmHg in E; mean DBP decreased from 100.3+/-4.2 to 86.1+/-6.5 mmHg in M and from 100.3+/-4.2 to 84.7+/-6.3 mmHg in E. Proteinuria remained unchanged in M (from 1.6+/-1.59 to 1.62+/-1.79 g/24h), and decreased significantly in E (from 1.37+/-1.45 g/24h to 1+/-1.55 g/24h). No significant difference was observed in the rate of renal function decline in the two groups. CONCLUSIONS: Manidipine was safe and effective, obtaining a significant reduction in SBP and DBP from baseline. Although patients treated with enalapril showed a better antiproteinuric response, the two treatments were equally effective in reducing the rate of CRF progression in patients without glomerular disease.

Aged↗
PubMedDate not supplied

Endothelial dysfunction and oxidative stress in chronic renal failure.

Uremic patients have an increased incidence of cardiovascular disease (CVD), endothelial dysfunction and oxidative stress that can contribute to cardiovascular (CV) events. To assess the relationship between endothelial dysfunction, oxidative stress and renal failure severity, we studied 40 patients (age 57 +/- 7 yrs, 24 males) affected by chronic kidney disease (CKD) K/DOQI stage 3-5 (serum creatinine (Cr) 5.6 +/- 2.2 mg/dL) on conservative treatment, 20 uremic patients (age 57 +/- 12 yrs, 13 males) on hemodialysis (HD) and 30 healthy controls (56 +/- 12 yrs, 20 males). Before and 2 hr after oral vitamin C (2 g) administration, we measured brachial artery endothelium-dependent vasodilation (flow mediated dilation (FMD)) to reactive hyperemia following 5 min of forearm ischemia and the response to sublingual glyceril trinitrate (GTN). Measurements were made by high-resolution ultrasound and computerized analysis. FMD was lower in CKD patients than in controls (5.3 +/- 2.2 vs. 6.9 +/- 2.8%; p<0.01) and was further reduced in HD patients (3.6 +/- 2.7; p<0.01 vs. CKD patients). Response to GTN was similar in all groups. FMD was related to Cr clearance (r=0.42; p<0.01) in CKD patients, while it related inversely to Kt/V(urea) (r=-0.52; p<0.05) in HD patients. After vitamin C administration, FMD was significantly enhanced in HD (4.7 +/- 2.4%; p<0.01 vs. baseline), but not in CKD patients. Response to GTN was unaffected. However, vitamin C load reduced oxidative stress markers, and increased plasma antioxidant capability in both groups. In conclusion, the reduced endothelium-dependent dilation in the brachial artery of CKD patients is related to renal failure severity. HD patients showed a more marked alteration, which seems to be related, at least in part, to increased oxidative stress.

Adult↗