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Biomedical subjects

E A Francischetti

Publications and source records attributed to E A Francischetti.

At least 19 recordsLinked to original sources
PubMed2006

Selective imidazoline agonist moxonidine in obese hypertensive patients.

Obesity is the major risk factor for the development of hypertension. This association accentuates the risk of cardiovascular disease, as it is frequently accompanied by the components of the metabolic syndrome. This randomised open parallel study evaluated the chronic effects of moxonidine--a selective imidazoline receptor agonist--on blood pressure, plasma catecholamines, leptin, insulin and components of the metabolic syndrome in obese hypertensives. Amlodipine was used as the control drug. Our results showed that moxonidine and amlodipine significantly reduced blood pressure when measured using the oscillometric method and 24-hour blood pressure monitoring. Moxonidine therapy decreased systolic blood pressure from 160.4 +/- 2.4 to 142.1 +/- 3.3 mmHg (p < 0.005) and diastolic blood pressure from 102.4 +/- 1.3 to 89.7 +/- 1.6 mmHg (p < 0.005) after 24 weeks of treatment. Moxonidine administration reduced the supine arterial plasma levels of adrenaline from 63.2 +/- 6.6 to 49.0 +/- 6.7 pg/ml (p < 0.005), the supine arterial plasma levels of noradrenaline from 187.9 +/- 10.7 to 149.7 +/- 13.2 pg/ml (p < 0.01) and the orthostatic venous plasma levels of noradrenaline from 258.6 +/- 25.0 to 190.3 +/- 16.4 pg/ml (p = 0.03). Those variables were not changed by amlodipine. The plasma levels of leptin and insulin 120 min after a glucose load decreased after moxonidine administration from 27.2 +/- 3.5 to 22.6 +/- 2.9 pg/ml (p < 0.05) and from 139.7 +/- 31.2 to 76.0 +/- 15.2 U/ml (p < 0.05), respectively. Amlodipine, however, did not modify those variables. This study showed a comparable reduction in blood pressure with both antihypertensive drugs. Moxonidine decreased sympathetic nervous activity, improved insulin resistance and reduced the plasma levels of leptin.

Adult↗
PubMed2006

Renal functional reserve in obesity hypertension.

The capacity to increase glomerular filtration rate in response to an acute oral protein load is known as the renal functional reserve; the loss of such capacity is used as a marker of hyperfiltration. This physiological response in obese hypertensives is not yet fully understood. We aimed to study the interdependent effects of obesity and hypertension on renal reserve, taking into account renal kallikrein and nitric oxide in the modulation of that parameter. Fourteen obese hypertensives (mean age, 50.5 +/- 0.9 years) and nine lean hypertensives (mean age, 50.6 +/- 2.7 years) were evaluated. Renal haemodynamics and the levels of serum nitric oxide and urinary kallikrein were assessed at baseline and after a protein load (1 g/kg of body weight). An increase in the following parameters was observed when comparing obese and lean hypertensives: basal glomerular filtration rate; renal plasma flow; and urinary kallikrein and nitric oxide levels (129.2 +/- 2.9 vs. 101.4 +/- 3.4 ml/min/1.73 m2; 587.5 +/- 18.2 vs. 502.8 +/- 16.7 ml/min/1.73 m2; 0.120 +/- 0.02 vs. 0.113 +/- 0.02 mU/ml; 23.2 +/- 0.8 vs. 19.5 +/- 1.2 mmol/ml, respectively). The renal reserve was lower in obese hypertensives when compared with that of lean hypertensives (4.1 +/- 0.5 vs. 11.8 +/- 0.8 ml/min, p < 0.005). After a protein load, contrasting with the lean group, inability to elevate the nitric oxide serum levels and a lower increase in urinary kallikrein were observed in the obese group. These data suggest that obese hypertensives lose renal reserve earlier in the evolution to renal dysfunction. This may be due to the defective modulation of renal vasodilatation mechanisms by renal kallikrein and nitric oxide production.

Dietary Proteins↗
PubMed2005

Effects of dual blockade of the renin angiotensin system in hypertensive type 2 diabetic patients with nephropathy.

AIM: To evaluate the effects of combined treatment of an ACE inhibitor and an angiotensin II receptor antagonist on parameters related to the progression of renal disease in type 2 diabetic patients. METHODS: 20 hypertensive type 2 diabetic patients with non-nephrotic proteinuria (0.5 - 3.0 g/day) and estimated creatinine clearance > or = 40 ml/min/1.73m2 were randomly assigned to be treated with perindopril 8 mg/day (Per), irbesartan 300 mg/day (Irb) or a combination of both with the same doses (Per + Irb). Each treatment phase lasting 16 weeks was preceded by a four-week washout period. Diuretics, clonidine and hydralazine were used as supplementary drugs for blood pressure control. Patients were evaluated at baseline and at the end of each treatment phase. RESULTS: 15 (3M/12F) patients completed all the phases. Use of Per, Irb and Per + Irb led to a reduction in 24-hour mean blood pressure of 6 mmHg, 4 mmHg and 4 mmHg, respectively. Changes in glomerular filtration rate were not significant at any phase. Renal plasma flow was significantly more elevated with Irb than Per. Treatment with both Irb and Per + Irb induced similar plasma renin elevation, but treatment with Per did not, suggesting escape. Plasma aldosterone was reduced only by treatment with Per + Irb (-36%, p < 0.02). Reduction in proteinuria during Per + Irb (-33%) was not significantly different from Per (-34%) or Irb (-22%). Urinary transforming growth factor beta1 (TGF-beta1) excretion was significantly reduced with both Irb (-24%, p < 0.05) and Per + Irb (-36%, p < 0.05) but not with Per (-11%, p = 0.60). CONCLUSION: Only combined therapy with irbesartan plus perindopril concurrently reduces plasma aldosterone, proteinuria and urinary TGF-beta1.

Adult↗
PubMed1999

A definite role for the kallikrein-kinin system in the renal hemodynamic response to an oral protein load during the aging process.

The effect of aging on the physiologic responses of renal plasma flow (RPF) and glomerular filtration rate to an acute oral protein load (renal reserve) is a poorly understood process. In this study of 37 healthy human volunteers, distributed among three groups (group 1: n = 13, age range 20-39 years; group 2: n = 13, age range 40-59 years; group 3: n = 11, age range 60-68 years), we evaluated the influence of age on some of the vasoactive systems such as plasma renin activity, urinary kallikrein, plasmatic prokallikrein, plasmatic kallikrein, and plasmatic kininogen on RPF and creatinine clearance (Ccr) in response to an acute oral protein load (1 g/kg body weight). The aging process diminished but did not cease the increments in RPF (group 1: 539.6 vs. 658.9 ml/min/1.73 m(2), p < 0. 001; group 2: 509.0 vs. 570.7 ml/min/ 1.73 m(2), p < 0.001; group 3: 453.9 vs. 506.0 ml/min/ 1.73 m(2), p < 0.001) and Ccr (group 1: 139. 7 vs. 166.5 ml/ min/1.73 m(2), p < 0.001; group 2: 126.6 vs. 142.2 ml/min/1.73 m(2), p < 0.001; group 3: 112.6 vs. 121.4 ml/min/ 1.73 m(2), p < 0.01) after a protein overload. The plasma renin activity did not change after a meat meal. On the other hand, all parameters regarding the kinin system changed significantly in the direction of increased bradykinin formation, despite aging (urinary kallikrein - group 1: 0.25 vs. 0.44 mU/ml, p < 0.005; group 2: 0.25 vs. 0.41 mU/ml, p < 0.005; group 3: 0.33 vs. 0.47 mU/ml, p < 0.005/plasmatic kininogen - group 1: 1.3 vs. 0.9 microg LBK/ml, p < 0.005; group 2: 1.1 vs. 0.7 microg LBK/ml, p < 0.005; group 3: 0.8 vs. 0.7 microg LBK/ml, p < 0.005). These findings indicate that: (1) the aging process narrows but does not cease the increment range in Ccr and RPF after acute oral protein ingestion; (2) increased bradykinin formation plays a definite role in the acute renal vasodilatory response, and (3) contrary to previous clinical studies, our results suggest that the renal reserve is progressively and significantly reduced during the aging process.

Adult↗
PubMed1997

The effects of isradipine and spirapril as monotherapy and combined therapy on blood pressure, renal hemodynamics, natriuresis, and urinary kallikrein in hypertensive nephropathy.

In this cross-over, double-blind study, 12 essential hypertensive patients (stage I, II, and III) with glomerular filtration rate (GFR) between 50 to 80 mL/min/1.73 m2, were submitted to 4 weeks of placebo followed by 12 weeks with isradipine SRO (IS) 5 mg, spirapril (SP) 6 mg, and isradipine plus spirapril (IS + SP). The study evaluated the effects of these drugs on GFR ((99m)Tc DTPA), effective renal plasma flow (ERPF) ((131)I-orthoiodohippurate), urinary sodium excretion (UNaV), urinary kallikrein excretion (UKal), urinary albumin excretion (UAE), and plasma renin activity (PRA). The three protocols significantly reduced mean blood pressure (128 v 107 mm Hg; 126 v 112 mm Hg; 129 v 104 mm Hg with IS, SP and IS + SP, respectively). ERPF and GFR did not change. UNaV increased significantly after IS (0.17 v 0.22 mEq/min) and IS + SP (0.18 v 0.24 mEq/min). UKal increased significantly after IS (58.6%) and IS + SP (53.6%). UAE decreased significantly only after SP. PRA increased significantly after IS (1.31 v 2.84 ng/mL/h), SP (1.10 v 2.15 ng/mL/h), and after IS + SP (1.23 v 3.21 ng/mL/min). In conclusion, IS, SP and IS + SP were effective in reducing blood pressure while keeping renal function stable. Only SP significantly decreased UAE. Enhanced UKal may have played a role in natriuresis observed after IS and IS + SP.

Aged↗
PubMed1996

Effects of magnesium on blood pressure and intracellular ion levels of Brazilian hypertensive patients.

Fifteen patients with uncomplicated mild to moderate primary hypertension (7 males, 8 females, age range 36-65 years) were submitted to a double blind randomized crossover study, receiving MgO 3 times a day at a daily dose of 1.0 g (600 mg/day of magnesium) and placebo for a period of 6 weeks. This was to test the effects of oral magnesium supplementation on blood pressure and sodium, potassium, calcium and magnesium intraerythrocyte concentrations. Concomitantly, plasma renin activity and serum aldosterone was also measured. Oral magnesium reduced significantly the systolic (delta = -7.6 mmHg, P < 0.05); diastolic (delta = -3.8 mmHg, P < 0.01) and mean blood pressure (delta = -5.9 mmHg, P < 0.01). After magnesium supplementation intraerythrocyte sodium concentration was reduced (delta = -0.55 mEq/l per cell, P < 0.01) and intraerythrocyte magnesium concentration was increased (delta = 1.20 mg/dl per cell, P < 0.01). The diminution of the blood pressure correlated positively with the reduction in intraerythrocyte sodium (r = 0.66, P < 0.01) after magnesium. However, our results have shown that the blood pressure response to oral magnesium was not homogeneous. Forty percent of our patients had their blood pressure effectively controlled (more than 10 mmHg reduction in mean blood pressure), being the hypotensive effect more evident in patients with recent hypertension and in those where the reduction in intraerythrocyte sodium was significantly greater than in the non-responder individuals. Intraerythrocyte potassium and calcium, serum aldosterone, plasma renin activity and urinary sodium excretion were maintained unchanged after magnesium supplementation. These data showed that oral magnesium supplementation may reduce the blood pressure, which can be partially explained by the decrease in intracellular sodium and augment in intracellular magnesium.

Administration, Oral↗
PubMed1995

[The effect of urapidil on blood pressure, renal hemodynamics, lipid and glucose metabolism].

PURPOSE: To evaluate the effects of urapidil on blood pressure (BP), renal hemodynamics and lipid and glucose metabolism, in patients with mild-to-moderate uncomplicated essential hypertension. METHODS: Fifteen hypertensive patients, aged 38-64 year-old were studied by ambulatory blood pressure monitoring system (ABPM). It was also evaluated: 1) the creatinine clearance; 2) the effective renal plasma flow by use of a single plasma sample after injection of orthoiodohippurate; 3) the serum triglycerides, cholesterol, and HDL-cholesterol; 4) blood levels of glucose and insulin. The urapidil dose ranged from 60 to 180 mg/day, according to the individual response. RESULTS: The values after four weeks washout-placebo and active treatment with urapidil showed: the systolic/diastolic BP was reduced from 157.7 +/- 6/108.0 +/- 2 on placebo to 140.4 +/- 4/97.3 +/- 3 mmHg (p < 0.05/p < 0.01) after urapidil, respectively, whereas heart rate was unchanged. The percentage of elevated systolic and diastolic BP values during 24h (BP load) was reduced from 60.9% to 54.4% and from 60.8% to 50.3%, respectively. Effective renal plasma flow, glomerular filtration rate, filtration fraction and renal vascular resistance were unaltered by treatment. Significant increase in HDL-cholesterol was observed (from 39.5 +/- 3.6 on placebo vs 49.2 +/- 4.8 mg/dl (p < 0.01) after urapidil. Total cholesterol, LDL-cholesterol and triglycerides levels were not modified with treatment. Circulating plasma glucose and insulin remained unchanged. CONCLUSION: Urapidil is an effective antihypertensive agent without deleterious effect on renal hemodynamics, lipid and glucose metabolism.

Adult↗
PubMed1995

Losartan potassium as initial therapy in patients with severe hypertension.

This 12-week, open-label study was conducted to gain experience with losartan potassium, an angiotensin II receptor antagonist, in patients with severe hypertension. Patients were either untreated or withdrawn from current therapy for at least 48 h before initiation of losartan 50 mg once daily. Patients were titrated to 100 mg as needed to achieve a goal of sitting diastolic blood pressure (SiDBP) 90 or 95 mm Hg. Hydrochlorothiazide (12.5 mg once daily titrated to 25 mg) was added and followed by either a dihydropyridine calcium channel blocker (CCB) and/or atenolol, if BP was not controlled. A total of 179 patients with a pretreatment mean baseline BP of 172 +/- 17/112 +/- 18 mm Hg enrolled in the trial and BP was recorded 24 h after dosing at baseline and weeks 2, 4, 8 and the final week (10-12 weeks). The mean reductions in SiDBP from baseline were 7.3, 9.3, 15.9 and 18.9 mm Hg, respectively, and these changes from baseline were statistically significant, P < 0.001. At the end of the trial, 22% of patients remained on losartan monotherapy, 30% required the addition of hydrochlorothiazide (HCTZ) and 31% required both HCTZ and a CCB; 11% required HCTZ and atenolol while 4% required HCTZ, a CCB and atenolol; 2% of patients were on regimens not specified by the protocol. SiDBP < 90 mm Hg was achieved in 68 patients by the final visit; 24% of these patients were treated with losartan monotherapy (50 or 100 mg), 41% achieved control with the addition of HCTZ (12.5 or 25 mg) and 24% required triple therapy which included losartan, HCTZ and a CCB. As assessed by the investigator, 25% of the patients in the study had drug-related clinical adverse experiences. Headache was the most frequently reported clinical adverse event (26% of patients). No clinically significant changes in laboratory parameters were observed. It is concluded that losartan potassium can be used as initial therapy for patients with severe hypertension and can be administered concurrently with hydrochlorothiazide, calcium channel blockers and atenolol.

Adolescent↗
PubMed1992

Renin-angiotensin-aldosterone system in normal and hypertensive pregnancy. Response to postural stimuli.

Most studies that have attempted to distinguish pregnancy-induced hypertension from chronic hypertension in pregnancy include arbitrary clinical definitions and morphological reports based on renal biopsy. To evaluate whether these conditions have different responses to stimuli to the renin-angiotensin-aldosterone system, we studied four normal nonpregnant women, eight normal pregnant women, 10 women with pregnancy-induced hypertension, and 14 with chronic hypertension in pregnancy, in the third trimester of pregnancy, after they had sequentially adopted the supine, the left lateral recumbent, and the orthostatic positions for 90 minutes each. Postural maneuvers did not significantly change mean arterial pressure in pregnancy-induced hypertensive or in normal pregnant women, although in chronic hypertensive women, a significant reduction in this parameter was observed in left lateral recumbency. The renin-angiotensin-aldosterone system was significantly less activated with women in the supine position in pregnancy-induced hypertensive and chronic hypertensive women; however, as opposed to pregnancy-induced hypertensive women, those with chronic hypertension reassumed their humoral response to upright posture, which was accompanied by a significant reduction in sodium excretion. The parallelism between plasma renin activity and aldosterone levels, absent in normal pregnancy, returned in pregnancy-induced hypertensive and chronic hypertensive women in the erect posture (r = 0.73, p less than 0.01; r = 0.68, p less than 0.01, respectively). These data suggest that the adoption of the left lateral recumbent position in pregnancy reduces mean arterial pressure only in chronic hypertensive women. Moreover, in chronic hypertension, the upright position provoked a significant response of the renin-angiotensin-aldosterone system. This effect was not observed in women with pregnancy-induced hypertension.

Adolescent↗
PubMed1992

Effects of long-term administration of isradipine on renal hemodynamics and sodium metabolism.

The objective of this double-blind, placebo-controlled study was to evaluate the effects of isradipine on renal hemodynamics and function. Ten patients with mild-to-moderate hypertension were given isradipine at 2.5 mg twice daily for 3 months after 4 weeks of placebo washout. Renal studies were performed 2 h after the morning administration of treatment. The results of these evaluations indicate that isradipine as monotherapy significantly reduced the mean arterial pressure, while the effective renal plasma flow was increased (+16%) and glomerular filtration rate remained virtually unchanged (-8.7 ml/min). The filtration fraction and renal vascular resistance decreased significantly. There was a significant decrease in the absolute rate of proximal sodium reabsorption, and a significant increase in the distal reabsorption. Clearance of sodium remained unchanged. In conclusion, monotherapy with low-dose isradipine was not only effective in controlling blood pressure, but also decreased the renal vascular resistance while avoiding glomerular hyperfiltration, and exerted a protective effect on renal hemodynamics. Natriuresis also remained stable despite the blood pressure reduction.

Calcium Channel Blockers↗
PubMed1986

Sodium and hypertension. Still a controversy in 1986.

Interpopulation studies support the hypothesis of a causal relationship between sodium consumption and arterial hypertension. However, although this association has been contradicted by intrapopulation studies, the correlation between sodium and hypertension appears to be genetically determined, as there are both sodium-sensitive and sodium-resistant individuals. Sodium is essential for the maintenance of extracellular and plasma volume equilibrium. It is controlled metabolically by the interaction of several biological systems such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the kallikrein-kinin and prostaglandin systems. Thus, sodium has a definite role in the mechanism involved in the pathophysiology of the predominantly volume-dependent forms of arterial hypertension. Recently, different structural substances with natriuretic effects have been identified. Natriuretic hormone is a non-peptide substance which inhibits the Na,K-ATPase in response to extracellular volume increase. This hormone acts on the renal tubular cells reducing sodium reabsorption, and at an arteriolar level elevating peripheral resistance by increasing smooth muscle tension. Mammalian atria contain various precursors of biologically active peptides, with potent natriuretic and diuretic effects. They are released in response to volume loading and atrial stretch. Although some data suggest an important role for these natriuretic substances in fluid volume and blood pressure control, their place in physiology and in abnormal clinical states should be more definitively clarified in the next few years.

Animals↗