Ariela Sacerdote

Oscillatory Potentials of the Electroretinogram in Hypertensive Patients

Because alteration of oscillatory potentials of the electroretinogram has been described in diabetic patients without signs of diabetic retinopathy as an early marker of changes in microcirculation, we studied the behavior of these potentials in patients with early-onset hypertension. Electroretinograms were recorded in 24 subjects with essential hypertension (blood pressure > 140/90 mm Hg) and in 9 age-matched normotensive control subjects (blood pressure < 140/90 mm Hg). Diabetes and ocular diseases were considered exclusion criteria. Sitting blood pressure was measured by a single investigator with a mercury sphygmomanometer after each subject had been at rest for 10 minutes. Funduscopic changes in all subjects did not exceed stage I World Health Organization classification. The oscillatory index was calculated by adding waves O1, O2, and O3 within the b wave of the electroretinogram. Statistical analysis was performed with Students t test for paired and unpaired data and linear regression. The oscillatory index was significantly reduced in hypertensive patients compared with normotensive subjects. An inverse relationship was observed when systolic and diastolic blood pressures were plotted against the oscillatory index. In conclusion, our data demonstrate that the electrical activity of the retina is altered early in the course of hypertension and that the influence of systolic pressure on the oscillatory index is greater than that of diastolic pressure.

Lacidipine prevents the hypertension and renal and cardiac changes induced by high-fructose diet in WKY rats.

Normotensive rats fed a high-fructose diet (HFD) develop hypertriglyceridemia, hyperinsulinemia, and hypertension. The glomerular changes observed in the kidneys of these animals are similar to those observed in diabetic rats. The aim of this study was to evaluate whether lacidipine, a calcium antagonist, could have a protective effect with this animal model. Forty male Wistar-Kyoto (WKY) rats were divided into four groups treated with HFD + placebo; HFD + lacidipine, 0.3 mg/kg/day; HFD + lacidipine, 3 mg/kg/day; or standard diet + placebo for 4 weeks. Urinary excretion of the stable metabolic products of nitric oxide (NO) was determined, because this vasoactive agent has been found to cause hemodynamic changes in the diabetic kidney. Glomerular size was determined by means of morphometric analysis. The results of this study show that lacidipine prevents (a) the HFD-induced increase in blood pressure in a dose-dependent manner; (b) the HFD-induced increase in glomerular size and fibronectin synthesis; and (c) the increase of collagen III synthesis in the heart. The drug had no effect on the increased urinary excretion of the stable metabolic products of NO. These data suggest that lacidipine might be useful in preventing the renal and cardiac damage caused by hypertension and non-insulin-dependent diabetes mellitus.

Neither physical exercise nor α1- and β-adrenergic blockade affect plasma endothelin concentrations

Endothelins (ET) are recently discovered vasoconstrictor agents released from endothelial cells and have been the object of intense investigation by researchers. Many of the factors that seem to influence the release of ET are modified by prolonged exercise. The purpose of this study was to investigate the effect of physical exercise on ET plasma concentrations and the effect of α. and β-blockade on ET concentrations at rest and during exercise. Fifteen young volunteers (age 20-35 years) performed an exercise test on a bicycle ergometer. The starting workload of 50 W was increased by 30 W every 3 min until maximal heart rate was achieved ; after a 2 min recovery period at 50 W the test continued for 15 min at 60% maximal work load. Blood samples were taken for ET determination before and after the test. After 1 week, the test was repeated. In the 2 days before either the first or the second test, each volunteer randomly received carvedilol (C) (25 mg), an α 1 -adrenoceptor and β-adrenoceptor blocker. There was no significant difference in ET concentrations after exercise with or without C administration (1.24 ± 0.66, 1.42 ± 0.83, 1.66 ± 1.15, 1.61 ± 0.87 pg/mL), showing that prolonged aerobic exercise does not affect plasma ET levels. Moreover, in our healthy young volunteers, blockade of α- and β-adrenoceptors had no effect on ET levels at rest and after exercise. Am J Hypertens 1996 ;9 :819-822

Involvement of the Renin Angiotensin System in the Pathogenesis of Postexercise Proteinuria

Proteinuria after strenuous exercise is common in healthy subjects. The pathophysiologic mechanism of postexercise proteinuria (PEP) is not clear, although the phenomenon has long been known and many explanatory theories have been proposed. It is widely recognized that angiotensin II may increase filtration of protein through the glomerular membrane, and that its concentration in plasma increases during exercise. The aim of this study was to evaluate possible involvement of angiotensin II in the pathogenesis of PEP. Of 25 young volunteers who performed maximal aerobic exercise, eight showed PEP. The exercise was repeated after an interval of at least one week, now 90 minutes after administration of captopril (25 mg). Captopril did not affect the achieved work load of the maximal blood pressure and heart rate during the exercise, but PEP was not found. As it was possible to prevent PEP by administering an angiotensin-converting enzyme inhibitor, the study supports the theory that the renin angiotensin system is involved in the pathogenesis of PEP.

Antihypertensive drugs and the nervous system : Ace-inhibitors restore oscillatory potentials in hypertensives

The authors have previously reported that oscillatory potentials (O.P.) of the electroretinogram are impaired in essential hypertensive patients before the appearance of funduscopic changes. They can therefore be considered an early marker of the nervous damage induced by hypertension. Aim of this study was to evaluate whether an antihypertensive regimen could influence the progression of this damage. O.P. were recorded in 35 essential hypertensives before antihypertensive treatment and after one-year treatment. The patients were randomly allocated into 4 treatment groups: 1) beta-blockers 2) ACE-Inhibitors 3) calcium antagonists 4) no pharmacological treatment. At the end of the study, blood pressure was significantly decreased in all but group 4. O.P., similar in the 4 groups at the beginning, were significantly higher at the end of the study only in patients treated with ACE-inhibitors. The results of this study suggest that although all hypotensive agents reduced blood pressure only ACE-I showed a protective effect on the retinal electric electrophysiology in hypertensive patients.

Effects of chronic treatment with losartan on blood pressure, endothelin-like immunoreactivity and nitric oxide in normotensive rats.

Background Losartan is a new angiotensin II type 1 (AT1) receptor antagonist and an antihypertensive drug. Nitric oxide is a vasodilating agent and endothelins are powerful vasoconstrictors, both synthesized by and released from endothelial cells. Angiotensin II promotes the release of endothelins in cultured cells and this effect is prevented by losartan. Nitric oxide is also synthesized in the macula densa; therefore this substance may affect the regulation of renin excretion. Objective The aim of the present study was to evaluate the effects of losartan on blood pressure, endothelin-like immunoreactivity and nitric oxide in normotensive rats. Materials and methods Male Wistar-Kyoto rats were divided into two groups. One group (n = 10) was treated with losartan at 10 mg/kg once a day by gavage for 4 weeks and a placebo group (n = 10) was given the same volume of water once a day by gavage. Blood pressure was measured weekly with a tail cuff and 24-h urine was collected at the beginning and at the end of the study. After 4 weeks all rats were killed and blood samples taken. Endothelin-like immunoreactivity was determined in plasma and urine using a 125I endothelin radioimmunuoassy kit. The stable metabolic products of nitric oxide, NO2- and NO3-, were measured in urine by the brucine method. Results After 4 weeks blood pressure was significantly lower in the losartan group (131 ± 4 versus 118 ± 6 mmHg, P = 0.001). Plasma endothelin-like immunoreactivity was similar in both groups while 24-h urinary endothelin-like immunoreactivity was significantly increased in the losartan group (29 ± 25, 32 ± 21, 43 ± 19, 72 ± 30 pg/24 h; F = 0.0003). NO2- and NO3- were unchanged in both groups. Conclusions Our data show that chronic AT1 receptor blockade does not modify plasma endothelin-like immunoreactivity but increases urinary endothelin-like immunoreactivity. The significance of this finding remains obscure. It may represent a compensatory mechanism against the sustained vasodilation caused by losartan. Nitric oxide does not seem to affect the antihypertensive effect of losartan, since the urinary excretion of nitric oxide metabolites was unchanged.

Metabolic effects of atenolol and doxazosin in healthy volunteers during prolonged physical exercise

Nonselective β-blockers may reduce exercise performance, not only through hemodynamic but also through metabolic effects. During prolonged physical exertion, lipolysis induced by plasma epinephrine occurs through β-adrenoceptors of adipocytes. Therefore, β-blockade may reduce release of free fatty acids (FFA) from adipocytes and consequently the energy supply for muscle cells. In this single-blind study, we compared the metabolic effects of atenolol with those of doxazosin, an α1-blocker, during exercise in 26 young volunteers (age 20–35 years). All subjects performed an exercise test on a bicycle ergometer 5 h after consuming a standard breakfast. The starting workload of 50 W was increased by 30 W every 3 min until maximal heart rate (HR) was achieved; after a 2-min recovery period at 50 W the test was continued for 15 min at 60% maximal workload. Before and at the end of the test, blood samples were taken for glucose, lactate, and FFA determination. After 1 week, the test was repeated; the volunteers randomly received atenolol or doxazosin for 2 days before the second test. Exercise performance, plasma glucose, and lactate were not affected by either drug. The concentration of FFA was unchanged in subjects treated with doxazosin but was significantly reduced after the test in subjects treated with atenolol. Our data demonstrate that neither doxazosin nor atenolol impairs exercise performance in young volunteers. Atenolol reduces plasma FFA concentration possibly by inhibiting lipolysis. Doxazosin, in contrast, does not alter this parameter. Therefore, doxazosin may be a antihypertensive drug of potential benefit in treatment of hypertensive patients engaging in sports or undergoing a program of physical training. Chronic studies performed in hypertensive patients are necessary to confirm this observation.

Nifedipine Reduces Postexercise Proteinuria in Young Volunteers

Previous studies have demonstrated that it is possible to prevent postexercise proteinuria with angiotensin-converting enzyme inhibitors. To determine whether calcium antagonists have the same effect, 40 young healthy volunteers underwent maximal aerobic exercise with and without nifedipine 10 mg per os 1 h before the first or second trial. Urinary excretion of albumin (UAE), transferrin (UTE) and alpha 1-microglobulin (UME) were examined before and after each trial. UAE, UTE and UME were significantly increased after exercise. Nifedipine significantly decreased UAE (p = 0.001) and UTE (p = 0.02) after exercise, and slightly decreased the maximal work load and the basal excretion of albumin. UME was unchanged. Therefore, the results of this study demonstrate that nifedipine administration before exercise significantly reduces postexercise proteinuria.