American Journal of Physiology-Endocrinology and Metabolism, 1994
We assessed in normal subjects the effects of an acute increase in forearm norepinephrine (NE) re... more We assessed in normal subjects the effects of an acute increase in forearm norepinephrine (NE) release, evoked by -20 mmHg lower body negative pressure (LBNP), on insulin-mediated muscle glucose uptake. Seven normal subjects underwent the following two insulin euglycemic clamps in random sequence: one during application of LBNP and the other without LBNP (control study). In the control study, hyperinsulinemia (approximately 60 microU/ml) produced a significant increment in forearm NE release, measured by using the forearm perfusion technique combined with infusion of tritiated NE (from 4.91 +/- 1 to 7.94 +/- 1.33 ng.l-1.min-1; P < 0.05). Forearm glucose uptake rose from 0.97 +/- 0.13 to 5.2 +/- 0.2 mg.l-1.min-1 in response to insulin infusion. When the insulin clamp was performed during LBNP, forearm NE release rose to significantly higher values than those of the control study (from 4.33 +/- 0.52 to 12.7 +/- 1.46 ng.l-1.min-1; P < 0.01 vs. control). Under these conditions, th...
The pressure-natriuresis curve which determines the long-term blood pressure (BP) level is diffic... more The pressure-natriuresis curve which determines the long-term blood pressure (BP) level is difficult to measure accurately in freely moving animals. The present work aimed to deaign e protocol which will allow auch a measure. It wee daveloped in LH and in low blood pressura (LL) control rats which wara ACE inhibited in order to suppress tha influence of spontaneous adaptationa of the renin angiotansin system. Mak LH and LL rata were traated from 3 weaks of age with an ACE inhibitor, parindopril (3 mg/kg/24h, P.o.). At 15 weeks of age, rats were placed in matabolic cagea, BP was racorded by talametry and 24h-urina was collected daily during 3 successive periods: 9 days of normal salt intake (standard diat containing 0.3% NaCl + water), 21 days of high salt intake (standard diet + 20/0 NaCl es a drinking solution), and 4 days of return to normal salt intake. While receiving a normal sail diet, perindopril-treated LH and LL rats axhibited similar mean BP and nattiuresia (82*2 va 77 i 3 mmHg; 2.09 + 0.16 vs 2.03 + 0.16 mmol/24h in LH and LL rats respectively). During high salt intake BP increased in both strains which allowed to calculata the slope of the pressure-natriuresis curva, In perindopril-treated LH rats compared to LL controls a significantly highar maan BP wes associated with a blunted pressure-natriurasis curve slope (155 + 6 w 104 + 2 mmHg p<O.01 and 0,53 * 0.04 vs 0.79 + 0.04 mmol/mmHg/24h pcO, Ol in LH and LL rats respectively). After the cassation of the high salt diet the BP raturned to pre-salt load values within 48 hra following pressure-nattiuresis curves which had similar slopes than those observed during tha salt load. In conclusion: 1) the above deacribad protocol allows to measura pressure-natriuresis in chronic conditions and in freely moving rats, 2) an early and chronic ACE inhibition prevents the development of hypertension in LH rats but does not allow them to maintain a normal BP in front of a high salt diet. This failure is associated with a blunted pressure-natriuresis curve slope.
Excessively high and low achieved blood pressure (BP) may be associated with a bad outcome in pat... more Excessively high and low achieved blood pressure (BP) may be associated with a bad outcome in patients with coronary artery disease, the J curve phenomenon. The effect of BP changes from baseline in relation with the subsequent risk of stroke and myocardial infarction (MI) is unknown. Of the 25 620 patients randomized in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, we selected 19 102 patients with coronary artery disease at baseline. BP at entry was 141/82 mm Hg, and its average decrease during follow-up was 7/6 mm Hg. BP entered the analysis as time-varying variable modeled with restricted cubic splines. After adjustment for several potential determinants of reverse causality, a change in BP from baseline by -34/-21 mm Hg (10th percentile) was associated with a lesser risk of stroke without any significant increase in the risk of MI. A rise in systolic/diastolic BP from baseline by 20/10 mm Hg (90th percentile) was associate...
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension, 2013
Numerous factors partake in the fine-tuning of arterial blood pressure. The heptahelical G-protei... more Numerous factors partake in the fine-tuning of arterial blood pressure. The heptahelical G-protein-coupled receptors (GPCRs) represent one of the largest classes of cell-surface receptors. Further, ligands directed at GPCRs account for nearly 30 % of current clinical pharmaceutical agents available. Given the wide variety of GPCRs involved in blood pressure control, it is reasonable to speculate for a potential role of established intermediaries involved in the GPCR desensitization process, like the G-protein-coupled receptor kinases (GRKs), in the regulation of vascular tone. Of the seven mammalian GRKs, GRK2 seems to be the most relevant isoform at the cardiovascular level. This review attempts to assemble the currently available information concerning GRK2 and hypertension, opening new potential fields of translational investigation to treat this vexing disease.
One of the most important causes of the unsatisfactory results of antihypertensive therapy in cur... more One of the most important causes of the unsatisfactory results of antihypertensive therapy in current medical practice is the difficulty in evaluating individual tolerability to the various antihypertensive agents. The methods commonly used, i.e. assessment in controlled studies of limited duration, or notification to pharmacovigilance authorities, clearly underestimate the problem. In order to obtain more correct information on antihypertensive practice, an Italian pharmacoepidemiological study has recently been planned, and the results of a pilot phase of this study are reported here.
Annali italiani di medicina interna : organo ufficiale della Società italiana di medicina interna, 1995
Several epidemiologic studies have demonstrated that hypertensive patients have an increased risk... more Several epidemiologic studies have demonstrated that hypertensive patients have an increased risk for the development of atherosclerosis. Although the appearance of atherosclerosis only in those parts of vascular system subjected to high blood pressure suggests that the mechanical stress is the principal factor involved in the development of atherosclerosis, the mechanisms underlying the linkage between hypertension and atherosclerosis are not yet completely understood. In fact, the evidence that antihypertensive treatments are not able to abolish the increased incidence of ischemic accidents in hypertensive patients suggests that other cellular and molecular mechanisms are involved in the pathogenesis of atherosclerosis. The pathogenesis of hypertension is a multifactorial process that involves the interaction of genetic and environmental factors which determine the abnormalities of volume regulation, the enhanced vasoconstriction and the remodeling of the arterial wall which is ch...
Archives des maladies du coeur et des vaisseaux, 1990
Left ventricular hypertrophy secondary to hypertension has been associated with a reduction of ma... more Left ventricular hypertrophy secondary to hypertension has been associated with a reduction of maximum coronary flow per unit mass as shown by the increase in the minimal threshold of coronary vascular resistance per gramme. This phenomenon has usually been attributed to an increase in muscle mass with absent or inadequate vascular compensation. However, chronic hypertension may induce a function reduction in coronary flow. In particular, it has been recently shown that coronary vascular resistances are influenced by a cardio-cardiac reflex involving the baroreceptor response. Left ventricular hypertrophy could alter the function of the ventricular receptors and favourise myocardial ischemia by preventing the adaptation of coronary flow to myocardial metabolic demands.
Mediterranean Journal of Nutrition and Metabolism, 2011
Efficacy of a new patented proprietary combination of natural nutraceuticals (PN) containing natu... more Efficacy of a new patented proprietary combination of natural nutraceuticals (PN) containing natural hypolipidemic as red yeast, policosanol and berberine was tested in a large study on dyslipidemic patients in clinical practice. A parallel, controlled, randomized, multicenter study was designed. After 2 weeks on a stable dietary regimen, the patients were randomized to PN 1 tablet/day associated with diet (PN ? D) or diet alone (D) for 16 weeks. Entry criteria were: Tot-Chol [200 mg/dL or LDL-Chol [150 mg/dL without a clear indication for statins, or plasma triglycerides [150 mg/dL. Lipid pattern and CV parameters were evaluated at baseline and monthly. 1,751 patients were enrolled in 248 Italian units, 933 patients on PN ? D and 818 on D. The baseline lipid values were: Tot-Chol 255.4 versus 243.1 mg/dL, LDL-Chol 170.1 versus 162.2 mg/dL, HDL-Chol 50.0 versus 48.8 mg/dL, and TG 190.5 versus 184.4 mg/dL. PN constantly and significantly improved lipid parameters versus D group: at 16 weeks-19.1 versus-9.4% for Tot-Chol (p \ 0.001),-23.5 versus-10.8% for LDL-Chol (p \ 0.001), ?11.6 versus ?4.0% for HDL-Chol (p \ 0.001),-17.9 versus-11.3% for TG (p \ 0.001). In conclusions, PN plus diet allows an effective improvement of blood lipids with a significant reduction of global CV risk, suggesting a role for PN in CHD prevention. Keywords Metabolic syndrome Á Nutraceuticals Á Berberine Á Red yeast Á Dyslipidemia The members of Armoweb Study Group has been given in the Appendix.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1997
This study compared the results of adenosine 99mTc-tetrofosmin cardiac tomography with those of a... more This study compared the results of adenosine 99mTc-tetrofosmin cardiac tomography with those of adenosine echocardiography in identifying patients with coronary artery disease (CAD) and in localizing individual stenosed, coronary vessels. Twenty-six consecutive patients with suspected or known CAD had simultaneous adenosine (140 micrograms/Kg/min intravenously) 99mTc-tetrofosmin tomography and two-dimensional echocardiography. All patients had coronary angiography within 4 wk from imaging studies. Regional 99mTc-tetrofosmin activity was quantitatively measured in 78 coronary vascular territories and echocardiographic left ventricular function was assessed in corresponding regions. At coronary angiography one patient had normal coronary vessels, 12 patients one-vessel and 13 had multivessel disease (> or = 50% luminal stenosis). Among the 25 patients with CAD, 22 showed perfusion defects at adenosine 99mTc-tetrofosmin tomography (sensitivity 88%) and 17 had abnormal echocardiograp...
American Journal of Physiology-Endocrinology and Metabolism, 1994
We assessed in normal subjects the effects of an acute increase in forearm norepinephrine (NE) re... more We assessed in normal subjects the effects of an acute increase in forearm norepinephrine (NE) release, evoked by -20 mmHg lower body negative pressure (LBNP), on insulin-mediated muscle glucose uptake. Seven normal subjects underwent the following two insulin euglycemic clamps in random sequence: one during application of LBNP and the other without LBNP (control study). In the control study, hyperinsulinemia (approximately 60 microU/ml) produced a significant increment in forearm NE release, measured by using the forearm perfusion technique combined with infusion of tritiated NE (from 4.91 +/- 1 to 7.94 +/- 1.33 ng.l-1.min-1; P < 0.05). Forearm glucose uptake rose from 0.97 +/- 0.13 to 5.2 +/- 0.2 mg.l-1.min-1 in response to insulin infusion. When the insulin clamp was performed during LBNP, forearm NE release rose to significantly higher values than those of the control study (from 4.33 +/- 0.52 to 12.7 +/- 1.46 ng.l-1.min-1; P < 0.01 vs. control). Under these conditions, th...
The pressure-natriuresis curve which determines the long-term blood pressure (BP) level is diffic... more The pressure-natriuresis curve which determines the long-term blood pressure (BP) level is difficult to measure accurately in freely moving animals. The present work aimed to deaign e protocol which will allow auch a measure. It wee daveloped in LH and in low blood pressura (LL) control rats which wara ACE inhibited in order to suppress tha influence of spontaneous adaptationa of the renin angiotansin system. Mak LH and LL rata were traated from 3 weaks of age with an ACE inhibitor, parindopril (3 mg/kg/24h, P.o.). At 15 weeks of age, rats were placed in matabolic cagea, BP was racorded by talametry and 24h-urina was collected daily during 3 successive periods: 9 days of normal salt intake (standard diat containing 0.3% NaCl + water), 21 days of high salt intake (standard diet + 20/0 NaCl es a drinking solution), and 4 days of return to normal salt intake. While receiving a normal sail diet, perindopril-treated LH and LL rats axhibited similar mean BP and nattiuresia (82*2 va 77 i 3 mmHg; 2.09 + 0.16 vs 2.03 + 0.16 mmol/24h in LH and LL rats respectively). During high salt intake BP increased in both strains which allowed to calculata the slope of the pressure-natriuresis curva, In perindopril-treated LH rats compared to LL controls a significantly highar maan BP wes associated with a blunted pressure-natriurasis curve slope (155 + 6 w 104 + 2 mmHg p<O.01 and 0,53 * 0.04 vs 0.79 + 0.04 mmol/mmHg/24h pcO, Ol in LH and LL rats respectively). After the cassation of the high salt diet the BP raturned to pre-salt load values within 48 hra following pressure-nattiuresis curves which had similar slopes than those observed during tha salt load. In conclusion: 1) the above deacribad protocol allows to measura pressure-natriuresis in chronic conditions and in freely moving rats, 2) an early and chronic ACE inhibition prevents the development of hypertension in LH rats but does not allow them to maintain a normal BP in front of a high salt diet. This failure is associated with a blunted pressure-natriuresis curve slope.
Excessively high and low achieved blood pressure (BP) may be associated with a bad outcome in pat... more Excessively high and low achieved blood pressure (BP) may be associated with a bad outcome in patients with coronary artery disease, the J curve phenomenon. The effect of BP changes from baseline in relation with the subsequent risk of stroke and myocardial infarction (MI) is unknown. Of the 25 620 patients randomized in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, we selected 19 102 patients with coronary artery disease at baseline. BP at entry was 141/82 mm Hg, and its average decrease during follow-up was 7/6 mm Hg. BP entered the analysis as time-varying variable modeled with restricted cubic splines. After adjustment for several potential determinants of reverse causality, a change in BP from baseline by -34/-21 mm Hg (10th percentile) was associated with a lesser risk of stroke without any significant increase in the risk of MI. A rise in systolic/diastolic BP from baseline by 20/10 mm Hg (90th percentile) was associate...
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension, 2013
Numerous factors partake in the fine-tuning of arterial blood pressure. The heptahelical G-protei... more Numerous factors partake in the fine-tuning of arterial blood pressure. The heptahelical G-protein-coupled receptors (GPCRs) represent one of the largest classes of cell-surface receptors. Further, ligands directed at GPCRs account for nearly 30 % of current clinical pharmaceutical agents available. Given the wide variety of GPCRs involved in blood pressure control, it is reasonable to speculate for a potential role of established intermediaries involved in the GPCR desensitization process, like the G-protein-coupled receptor kinases (GRKs), in the regulation of vascular tone. Of the seven mammalian GRKs, GRK2 seems to be the most relevant isoform at the cardiovascular level. This review attempts to assemble the currently available information concerning GRK2 and hypertension, opening new potential fields of translational investigation to treat this vexing disease.
One of the most important causes of the unsatisfactory results of antihypertensive therapy in cur... more One of the most important causes of the unsatisfactory results of antihypertensive therapy in current medical practice is the difficulty in evaluating individual tolerability to the various antihypertensive agents. The methods commonly used, i.e. assessment in controlled studies of limited duration, or notification to pharmacovigilance authorities, clearly underestimate the problem. In order to obtain more correct information on antihypertensive practice, an Italian pharmacoepidemiological study has recently been planned, and the results of a pilot phase of this study are reported here.
Annali italiani di medicina interna : organo ufficiale della Società italiana di medicina interna, 1995
Several epidemiologic studies have demonstrated that hypertensive patients have an increased risk... more Several epidemiologic studies have demonstrated that hypertensive patients have an increased risk for the development of atherosclerosis. Although the appearance of atherosclerosis only in those parts of vascular system subjected to high blood pressure suggests that the mechanical stress is the principal factor involved in the development of atherosclerosis, the mechanisms underlying the linkage between hypertension and atherosclerosis are not yet completely understood. In fact, the evidence that antihypertensive treatments are not able to abolish the increased incidence of ischemic accidents in hypertensive patients suggests that other cellular and molecular mechanisms are involved in the pathogenesis of atherosclerosis. The pathogenesis of hypertension is a multifactorial process that involves the interaction of genetic and environmental factors which determine the abnormalities of volume regulation, the enhanced vasoconstriction and the remodeling of the arterial wall which is ch...
Archives des maladies du coeur et des vaisseaux, 1990
Left ventricular hypertrophy secondary to hypertension has been associated with a reduction of ma... more Left ventricular hypertrophy secondary to hypertension has been associated with a reduction of maximum coronary flow per unit mass as shown by the increase in the minimal threshold of coronary vascular resistance per gramme. This phenomenon has usually been attributed to an increase in muscle mass with absent or inadequate vascular compensation. However, chronic hypertension may induce a function reduction in coronary flow. In particular, it has been recently shown that coronary vascular resistances are influenced by a cardio-cardiac reflex involving the baroreceptor response. Left ventricular hypertrophy could alter the function of the ventricular receptors and favourise myocardial ischemia by preventing the adaptation of coronary flow to myocardial metabolic demands.
Mediterranean Journal of Nutrition and Metabolism, 2011
Efficacy of a new patented proprietary combination of natural nutraceuticals (PN) containing natu... more Efficacy of a new patented proprietary combination of natural nutraceuticals (PN) containing natural hypolipidemic as red yeast, policosanol and berberine was tested in a large study on dyslipidemic patients in clinical practice. A parallel, controlled, randomized, multicenter study was designed. After 2 weeks on a stable dietary regimen, the patients were randomized to PN 1 tablet/day associated with diet (PN ? D) or diet alone (D) for 16 weeks. Entry criteria were: Tot-Chol [200 mg/dL or LDL-Chol [150 mg/dL without a clear indication for statins, or plasma triglycerides [150 mg/dL. Lipid pattern and CV parameters were evaluated at baseline and monthly. 1,751 patients were enrolled in 248 Italian units, 933 patients on PN ? D and 818 on D. The baseline lipid values were: Tot-Chol 255.4 versus 243.1 mg/dL, LDL-Chol 170.1 versus 162.2 mg/dL, HDL-Chol 50.0 versus 48.8 mg/dL, and TG 190.5 versus 184.4 mg/dL. PN constantly and significantly improved lipid parameters versus D group: at 16 weeks-19.1 versus-9.4% for Tot-Chol (p \ 0.001),-23.5 versus-10.8% for LDL-Chol (p \ 0.001), ?11.6 versus ?4.0% for HDL-Chol (p \ 0.001),-17.9 versus-11.3% for TG (p \ 0.001). In conclusions, PN plus diet allows an effective improvement of blood lipids with a significant reduction of global CV risk, suggesting a role for PN in CHD prevention. Keywords Metabolic syndrome Á Nutraceuticals Á Berberine Á Red yeast Á Dyslipidemia The members of Armoweb Study Group has been given in the Appendix.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1997
This study compared the results of adenosine 99mTc-tetrofosmin cardiac tomography with those of a... more This study compared the results of adenosine 99mTc-tetrofosmin cardiac tomography with those of adenosine echocardiography in identifying patients with coronary artery disease (CAD) and in localizing individual stenosed, coronary vessels. Twenty-six consecutive patients with suspected or known CAD had simultaneous adenosine (140 micrograms/Kg/min intravenously) 99mTc-tetrofosmin tomography and two-dimensional echocardiography. All patients had coronary angiography within 4 wk from imaging studies. Regional 99mTc-tetrofosmin activity was quantitatively measured in 78 coronary vascular territories and echocardiographic left ventricular function was assessed in corresponding regions. At coronary angiography one patient had normal coronary vessels, 12 patients one-vessel and 13 had multivessel disease (> or = 50% luminal stenosis). Among the 25 patients with CAD, 22 showed perfusion defects at adenosine 99mTc-tetrofosmin tomography (sensitivity 88%) and 17 had abnormal echocardiograp...
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