BACKGROUND: In the BIGPRO 1 trial, one year of treatment with metformin in non-diabetic obese subjects with a central fat distribution had no significant effect on fasting plasma triglyceride concentration or on blood pressure despite a decrease in weight, fasting plasma insulin and glucose concentrations. To re-evaluate the effect of metformin on fasting triglyceride concentration and on blood pressure, the BIGPRO 1.2 trial included non-diabetic men (n=168) with a fasting plasma triglyceride concentration > or =1.7 and < or =6.5 mmol/l, high blood pressure (systolic > or =140 and < or =180 and/or diastolic > or =90 and < or =105 mmHg, or treatment for hypertension) and a waist-to-hip ratio > or =0.95. METHODS: A randomised double-blind trial comparing metformin treatment (850 mg bid) with placebo. RESULTS: Metformin had no significant effect either on blood pressure or plasma triglyceride concentration. In comparison with the placebo group, fasting plasma insulin (p<0.04), total cholesterol (p<0.05) and Apo B (p<0.008) concentrations decreased more in the metformin group in the BIGPRO 1. 2 trial, confirming most of the previous results of the BIGPRO 1 trial. Tissue plasminogen activator antigen concentration decreased significantly (p<0.01) only in the metformin group, but this was not significantly different from the placebo group (p<0.12); further, there were no significant differences in the change in plasminogen activator inhibitor 1. CONCLUSIONS: The consistency of the two BIGPRO trials supports the conclusion that metformin affects several cardiovascular risk factors favourably in non-diabetic subjects with a central fat distribution.

Adipose Tissue↗

PubMedDate not supplied

Neuronal metabolism of catecholamines: plasma DHPG, DOMA and DOPAC.

Pre-synaptic endings of the sympathetic nervous fibers control the metabolism of catecholamines, particularly inactivating norepinephrine after its neuronal recapture. The present study was carried out to investigate this segment of the metabolism of catecholamines through measurements of DHPG, DOMA and DOPAC concentrations in plasma. A sensitive and specific radio-enzymatic assay was developed of which the major characteristic is to include the plasma sample in the incubation mixture without initial extraction of the deaminated metabolites. In the rat, there was a statistically significant correlation between norepinephrine and DHPG in both anesthetized and conscious conditions and after clonidine or guanethidine induced reduction of sympathetic activity; thus it can be suggested that plasma DHPG is a good index of neuronal metabolism of norepinephrine in this animal. In humans, our data indicate an interesting correlation between norepinephrine and DOMA concentrations in plasma in resting conditions and within three hours after clonidine. Further studies need to be carried out to establish whether DOMA is a better index of neuronal metabolism of norepinephrine than DHPG.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

[Dominant polycystic renal disease. Study of 105 cases].

The study concerns 105 cases of dominant polycystic kidney disease. Affected relatives were observed in 65% of patients. The clinical features that leads to diagnosis were lumbar pain in 37.5% of cases, renal failure in 24.6% of cases and hypertension in 15.1% of cases. Hypertension was observed in 46.7% of cases and it seems that its onset is independent of chronic renal failure. Its frequency is of 55.1% when only kidneys were affected and of 21.4% when the liver was affected too. The progression of chronic renal failure is influenced by hypertension.

Adult↗

PubMedDate not supplied

Adrenaline hypothesis: effect of formoterol on noradrenaline release.

1 Originally, the so-called 'adrenaline hypothesis' related the release of noradrenaline (NA) to stimulation of presynaptic beta2-receptors in nerve endings; now it confers a possible role to adrenaline taken up then released by nerves endings. It represents a potentially useful therapeutic pathway. The present study aims to investigate the effects of formoterol, a highly selective beta2-adrenoceptor agonist. 2 It was carried out in freely moving rats, the isotope dilution technique being used to measure the NA spill over rate (NA-SOR) and metabolic clearance rate (MCR). 3 A series of three results are reported. (a) When compared with adrenaline on equimolar basis, formoterol (2.3 micro kg-1 min-1) increased NA-SOR while mean arterial blood pressure was decreased and heart rate increased. Thus, it was difficult to separate a direct presynaptic effect from indirect baroreflex-dependent activation of the sympathetic system. (b) When formoterol was infused at 1 ng kg-1 min-1, a dose empirically defined to induce no haemodynamic effect, NA-SOR was significantly increased, while NA-MCR remained unchanged. (c) The NA-SOR response to formoterol was not amplified by the presynaptic alpha2-adrenoceptor blocker, yohimbine, in contrast to the NA-SOR response to adrenaline. 4 In conclusion, formoterol, a beta2-adrenoceptor agonist, is shown to increase the release and plasma concentration of NA while its clearance was not changed.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Endothelium-dependent changes in arterial diameter in old normotensive rats.

1. In normotensive rats, removal of carotid artery endothelium results in an acute increase in diameter. This finding, observed in young animals, has not been investigated in old animals. The present study was undertaken to assess the contribution of endothelial function in the regulation of arterial stiffness in aged rats. 2. In normotensive female WAG/Rij rats, isobaric (100 mmHg transmural pressure) carotid diameter was measured in vitro in situ, using a previously described arterial preparation associated with a high-resolution echotracking technique allowing non-invasive diameter measurements under baseline conditions, after removal of the endothelium and after total relaxation of vascular smooth muscle by potassium cyanide. Histomorphometry of the carotid wall was studied after pressure fixation (100 mmHg) of the arteries. 3. Compared with younger animals (10 months), older animals (30 months) had the same baseline carotid isobaric diameter but significantly higher values of wall thickness and collagen content. In older animals, whereas total relaxation by potassium cyanide was associated with a slight but significant increase of isobaric diameter, no increase was observed after endothelium removal. 4. The results of the presnt study provide evidence that, in old normotensive rats, endothelium-dependent increases in isobaric carotid diameter are blunted. This endothelium alteration may contribute to the age-dependent increase in isobaric carotid stiffness observed in old rats.

Aging↗

PubMedDate not supplied

Clinical pharmacology of prazosin in hypertensive patients with chronic renal failure.

The clinical pharmacology of prazosin was studied in 10 hypertensive patients with chronic renal failure (group I) and in 9 hypertensive patients with normal renal function (group II). Prazosin, 2 mg, was given orally and blood samples were drawn at intervals for spectrofluorimetric assay. Blood pressure and heart rate were obtained at the same time. In the renal failure group, prazosin induced a significant decrease in systolic and diastolic blood pressures (-19 and -23%, respectively) at 90 min after intake, and these alterations were more rapid and marked than in the normal renal function group. Peak plasma concentration (Cmax) was higher (33.5 +/- 3.7 vs. 20.04 +/- 1.7 micrograms/liter, p < 0.01) and occurred earlier (1.3 +/- 0.2 vs. 2.7 +/- 0.3 hr, p < 0.005) in group I than in group II. The area under the plasma concentration-time curve (AUC0 infinity) was increased in the renal failure group (206.1 +/- 31.1 vs. 112.4 +/- 9.4 micrograms/hr/liter, p < 0.01). Apparent plasma elimination half-life (t 1/2) was not significantly different in the two groups (3.6 +/- 0.4 vs. 2.9 +/- 0.3 hr. ns). The mean blood pressure change (delta MBP%) was significantly correlated with the plasma level of prazosin in the renal failure group (n = 97, r = 0.489, p < 0.001) but not in patients with normal renal function (n = 74, r = 0.297, ns). The hypotensive action of prazosin is greater in patients with chronic renal failure, and the bioavailability or distribution of the drug is altered. Therefore, prazosin dosages should be modified in patients with impaired renal function.

Adult↗

PubMedDate not supplied

Direct vascular actions of methyclothiazide and indapamide in aorta of spontaneously hypertensive rats.

In vitro experiments were designed to assess the inhibitory effect of the thiazide diuretics methyclothiazide (MCTZ), the hydrochlorothiazide (HCTZ), and the thiazide-related diuretic indapamide (IND) on contractile responses to norepinephrine (NE) and arginine vasopressin (AVP) of aortic rings from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Changes in the tension of aortic ring preparations were measured isometrically. MCTZ (10(-4) M) induced endothelium-dependent inhibition of the vasoconstrictor responses to NE and AVP only in aortas from SHR, and the maximal vasoconstrictive effect of NE and AVP was decreased by 59 +/- 11% and 32.3 +/- 13%, respectively. Indapamide (10(-4) M) also induced endothelium-dependent inhibition of the contractile response to AVP in aortic rings from SHR, and the maximal vasoconstrictive effect of AVP was decreased by 33 +/- 5%. In contrast, HCTZ did not inhibit the contractile response to either NE or AVP, even at the highest concentration. This study provides evidence that methyclothiazide and indapamide inhibit the contractile response induced by norepinephrine and/or arginine vasopressin on SHR aortic preparations via an endothelium-dependent mechanism.

Animals↗

PubMedDate not supplied

Noninvasive measurement of medium-sized artery intima-media thickness in humans: in vitro validation.

Recent research in ultrasound technology has led to the development of a high-resolution echo-tracking device. The present study was performed to evaluate the accuracy in the measurement of human radial artery intima-media thickness with this new device. We determined the correlation between histological and ultrasonic measurements of intima-media thickness in 15 radial artery segments obtained from the distal end of the wrist-elbow harvest for coronary bypass grafting in patients with coronary heart disease. For arterial intima-media thickness, a positive correlation was observed between ultrasonic and histological measurements (r = 0.618; p < 0.014), and the difference between ultrasound and histology measurements was 41 +/- 66 microns, with the higher measurements found by the ultrasonic device. In a subgroup of 11 patients, we determined the correlation between in vivo ultrasonic measurements of radial artery intima-media thickness at the preoperative stage and in vitro ultrasonic measurements of intima-media thickness obtained postoperatively in the same arterial segments. Internal diameter was larger in vivo than in vitro, and intima-media thickness was smaller in vivo than in vitro. The cross-sectional area of the arterial wall was calculated from internal diameter and intima-media thickness. In vitro wall cross-sectional area was correlated with in vivo wall cross-sectional area (r = 0.929; p < 0.0001). Repeatability of in vivo intima-media thickness measurements was investigated in 10 subjects through the calculation of the repeatability coefficient as defined by the British Standards Institution.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗

PubMedDate not supplied

The wall to lumen ratio of the radial artery in patients with Raynaud's phenomenon.

The pathophysiology of Raynaud's phenomenon (RP) remains an enigma. Whatever theories proposed, the final event leading to the clinical symptoms is the occlusion of digital vessels. However, the possibility that the upstream large arterial vessels contribute to vasopasm has never been investigated. We used a high resolution echo-tracking device to calculate lumen diameter, wall thickness, and circumferential wall stress upstream the digital arteries, i.e. at the site of the radial artery. Fifteen control women, 15 age-matched women with primary RP (PRP) and 15 women presenting with a secondary RP due to systemic sclerosis (SSc) were included in the study. All vasodilating agents were discontinued 72 h before the study session, which was conducted in a room with a stable ambient temperature of 22 degrees C. Radial artery internal diameter, intima-media wall thickness, and mean arterial pressure were measured simultaneously. Internal diameter of patients with RP was significantly decreased (p < 0.001 vs. controls) whereas intima-media wall thickness and mean arterial pressure were closely similar in the three groups, resulting in an increase in the wall to lumen ratio. Thus, circumferential wall stress was significantly smaller (p < 0.05 vs. controls) in patients with RP. In conclusion, this study demonstrates that in patients with RP, wall to lumen ratio is increased and circumferential wall stress is reduced at the level of the radial artery. It is suggested that the geometrical and mechanical changes of this artery may favor the downstream occlusive phenomena observed in patients with PRP and SSc.

Adult↗