Massimiliano Fazio

Control of glomerular hyperfiltration and renal hypertrophy by an angiotensin converting enzyme inhibitor prevents the progression of renal damage in hypertensive diabetic rats.

OBJECTIVE Glomerular hyperfiltration and renal hypertrophy are both considered important in the progression of diabetic nephropathy. The aim of this study was to compare the effects of an equivalent reduction in blood pressure produced by the angiotensin-converting enzyme (ACE) inhibitor spirapril (SPI) and an antihypertensive triple drug combination of hydralazine, reserpine and hydrochlorothiazide (HRH) on kidney function, proteinuria and renal structure in hypertensive diabetic rats. DESIGN AND METHODS Four groups of animals were evaluated in short-term and long-term studies. In both studies one group served as a non-diabetic hypertensive control (H). The other three groups were rendered diabetic and were allocated to one of the following groups: the first diabetic group received no specific therapy (HD), the second diabetic group was treated with SPI (HD-SPI) and the third diabetic group was treated with HRH (HD-HRH). In each of the two studies the systolic blood pressure (SBP), 24 h urinary total protein, glomerular filtration rate (GFR), glomerular area, proximal tubular area and glomerular sclerosis were evaluated. RESULTS The blood pressure reduction was equal in rats receiving either SPI or HRH. The GFR, proteinuria, glomerular area and tubular area were significantly increased in the HD group, both in the short-term and the long-term study. In the HD-SPI group the diabetic hyperfiltration and renal hypertrophy responses were prevented. In the HD-HRH group the GFR and proteinuria were slightly reduced in the later phases of diabetes, while the glomerular area and tubular area were not affected. Semiquantitative analysis of renal lesions showed that SPI was more effective than HRH in the prevention of the development of glomerulosclerosis. CONCLUSIONS The results of this study suggest that the control of early adaptive hyperfiltration and renal hypertrophy by SPI may be relevant in the prevention of glomerulosclerosis.

Haemoconcentration, shear-stress increase and carotid artery diameter regulation after furosemide administration in older hypertensives

The aim of the present study was to determine whether changes of carotid wall shear stress induced by changes in blood viscosity after diuretic administration cause carotid arterial dilatation in elderly hypertensives, as reported in the cat. Arterial wall shear rate (ultrasound technique, profilmeter FRP III), the systo-diastolic diameter (echotracking technique) and the mean blood flow velocity and volume of the common carotid artery, the blood viscosity (rotational viscometer) and the finger arterial blood pressure (Finapress Ohmeda) were measured in 12 young volunteers (aged 25+/-2 years) and in 12 elderly hypertensives (aged 80+/-4 years) treated with short-acting calcium antagonists up to 24h before the study, both at baseline and after intravenous furosemide infusion (0.5mg/min), when the haematocrit had increased by at least two percentage points. After furosemide administration the mean arterial blood pressure decreased and blood viscosity and carotid systolic shear stress increased in both groups. However, common carotid artery diameter increased only in the young controls but not in the elderly hypertensives. These data show that an increase in carotid shear stress caused by haemoconcentration induces carotid vasodilatation only in young healthy subjects, and not in elderly hypertensives. This effect may be related to impaired endothelium function and/or arterial wall mechanics.

Large-Artery Hemodynamics After Acute Alcohol Administration in Young, Healthy Volunteers

The objective of the present study was to investigate the acute effects of alcohol on blood flow volume and velocity, on wall motion of superficial large arteries, and on systemic hemodynamics in humans. In 10 healthy volunteers small doses of alcohol were administered either orally (0.3 g/kg in 250 mL water) or intravenously (7.5 mg/kg/minute in 250 mL saline in 40 minutes). The effects of alcohol were compared with those of saline 250 mL infused for 40 minutes (6.25 mL/min). Blood velocity and systodiastolic changes of wall diameter were measured in the common carotid, femoral, and brachial arteries simultaneously with cardiac output and finger blood pressure. Skin temperature was measured at the cheek, hand, and toe. Ethanol administration caused a transitory blood pressure increase accompanied by a rise in peripheral resistances at 20 minutes. Arterial blood flow was not changed by either mode of alcohol administration at any of the measurement sites. However, this result was achieved through different compensatory mechanisms in each artery. In fact, mean carotid diameter increased after both oral and intravenous ethanol administration but remained unchanged at the brachial and femoral level. Mean blood velocity was reduced after alcohol administration at the carotid but was unchanged at the brachial and femoral level after oral or intravenous alcohol administration. Skin temperature increased 20 minutes after alcohol administration at all sites. This study shows that although acute alcohol administration does not change blood flow in superficial large arteries, it causes different autoregulatory local responses of vessel walls.

Baroreceptor-heart rate reflex sensitivity enhancement after urinary bladder distention in essential hypertensives

Abstract Our objective was to determine if urinary bladder distention modifies the sensitivity of the baroreceptor-heart rate reflex in hypertensive and control subjects. The baroreceptor-heart rate reflex sensitivity was measured in 15 male patients (mean age 37 ± 8 years) with mild untreated hypertension (mean 163 ± 8/95 ± 12 mmHg) and 17 age- and sex-matched control subjects before and after urinary bladder distention. Bladder filling was performed infusing saline heated to 37°C via a urinary catheter; the volume infused in each patient corresponded to that which caused the urge to void without reaching the pain threshold. The baroreceptor-heart rate reflex sensitivity was determined correlating the variations of the systolic pressure and of the peak blood flow velocity in the common carotid artery with the variations of the ECG RR′ interval of the following heart beat, both during spontaneous and phenylephrine-induced fluctuations of the haemodynamic variables. After bladder distention the diastolic pressure of the hypertensive subjects increased significantly (95 ± 12 vs. 100 ± 12 mmHg; P < 0.02), whereas the heart rate decreased (RR=873 ± 70 vs. 926 ± 80 ms; P < 0.005). These parameters were unchanged in the normotensive subjects (84 ± 9 vs. 83 ± 8 mmHg and 914 ± 158 vs. 913±140 ms, respectively). The baroreceptor-heart rate reflex sensitivity, measured on the basis of spontaneous pressure and carotid blood flow velocity fluctuations in relationship to RR changes, decreased in the normotensive subjects after bladder distention (10.7 ± 4.6 vs. 9.4 ± 2.7 ms/mmHg; P < 0.05 and 423 ± 99 vs. 356 ± 102 ms/kHz; P < 0.01, respectively), whereas it increased in the hypertensive patients (6.9 ± 3.6 vs. 8.3 ± 2.8 ms/mmHg; P < 0.03, and 332 ± 86 vs. 381 ± 97 ms/kHz; P < 0.03 respectively). After bladder distention and phenylephrine administration the baroreceptor-heart rate reflex sensitivity, measured by the correlation between systolic pressure and RR interval, increased only in the hypertensive group (10.2 ± 5.4 vs. 15.2 ± 7.7 ms/mmHg; P < 0.005). In conclusion urinary bladder distention provokes in hypertensives but not normotensive controls a brisk parasympathetic response of the component of the baroreceptor-heart rate reflex which controls heart rate.