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Biomedical subjects

A Pirrelli

Publications and source records attributed to A Pirrelli.

At least 19 recordsLinked to original sources
PubMed1996

Carrier-mediated transport controls hydroxyproline catabolism in heart mitochondria from spontaneously hypertensive rat.

In this study we have investigated hydroxyproline transport in rat heart mitochondria and, in particular, in heart left ventricle mitochondria isolated from both spontaneously hypertensive and Wistar-Kyoto rats. Hydroxyproline uptake by mitochondria, where its catabolism takes place, occurs via a carrier-mediated process as demonstrated by the occurrence of both saturation kinetics and the inhibition shown by phenylsuccinate and the thiol reagent mersalyl. In any case, hydroxyproline transport was found to limit the rate of mitochondrial hydroxyproline catabolism. A significant change in Vmax and Km values was found in mitochondria from hypertensive/hypertrophied rats in which the Km value decreases and the Vmax value increases with respect to normotensive rats, thus accounting for the increase of hydroxyproline metabolism due to its increased concentration in a hypertrophic/hypertensive state.

Animals↗
PubMed1996

[Aging and isomyosin pattern of the left ventricle in spontaneously hypertensive and Wistar Kyoto rats].

Changes of the contractile proteins in the left ventricle from spontaneously hypertensive rats (SHR) are extensively documented with the development of the hypertensive state and with ageing. This study was undertaken to determine whether also the left ventricle from normotensive rats exhibits age-related changes of the myosin pattern. The relative distribution of myosin isoforms was investigated in Wistar Kyoto (WKY, n = 50) and SHR (n = 50), both at the 5th, 9th, 24th, 48th and the 72nd week of life. A significant decrease in V1 as well as an increase in V3 percentage values, compared to the data obtained at the 5th week were observed in SHR from the 9th week, concomitantly to the rise in blood pressure values. These changes were more consistent with ageing (5 weeks: V1 99.0 +/- 0.9%, V2 0.6 +/- 0.1%, V3 0.4 +/- 0.3%; 72 weeks: V1 5.3 +/- 3.9%, V2 3.0 +/- 2.7%, V3 91.7 +/- 9.7%). In WKY rats, a significant decrease in V1 percentage values was detected at the 24th week and it was evident till the 72nd week. V3 significantly changed only at the 48th and the 72nd week (5 weeks: V1 100.0 +/- 0.0%; 72 weeks: V1: 41.4 +/- 6.5%, V2 13.3 +/- 2.8%, V3 45.5 +/- 6.9%). The results of this study confirm that alterations in the left ventricle isomyosin pattern occur early in SHR with the rise in blood pressure values and the increase in left ventricular mass. In contrast, modifications in the myosin isoform distribution were found only in WKY with ageing. These findings may be related to the biochemical changes occurring in the myocardial tissue either gradually, during the advanced ages of life, or early due to the hypertensive state.

Aging↗
PubMed1995

Left ventricular hypertrophy in spontaneously hypertensive rat: effects of ACE-inhibition on myocardiocyte ultrastructure.

The aim of this study is to investigate the effects of two ACE-inhibitors with different chemical formulae, cilazapril (CLZ) and captopril (CPT), on left ventricular myocardiocytes from spontaneously hypertensive rats (SHR), characterized by ultrastructural alterations associated with left ventricular hypertrophy, and from Wistar-Kyoto (WKY) rats, considered as controls. After CLZ-treatment, not remarkable changes are observed in WKY myocardiocytes, whereas SHR ones show a considerable reduction in their original alterations in ultrastructure. After CPT-treatment, both SHR and WKY myocardiocytes are altered in ultrastructure. The morphometric investigation confirms that CPT and CLZ produce different effects. Even if the drugs induce a similar decrease in blood pressure and left ventricular mass index, CLZ unlike CPT seems to improve the ultrastructural abnormalities associated with left ventricular hypertrophy. These changes could be related to the different chemical structure of CLZ and CPT, or to a different affinity of the two drugs for the local renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Antihypertensive treatment with verapamil and amlodipine. Their effect on the functional autonomic and cardiovascular stress responses.

Many biological and psychological factors induce haemodynamic and extra-cardiovascular functional changes mediated by the autonomic nervous system. Pharmacological blood pressure reduction, as a neurovegetative stimulus, can change the arousal of the sympathetic nervous system. We evaluated the effects of two calcium channel blockers, verapamil and amlodipine, both administered as monotherapies, upon the sympathetic stress response in 23 randomized mild-to-moderate essential hypertensives (161 +/- 2/98 +/- 1 mmHg). Patients performed four stress tests (mental arithmetic, colour word Stroop, cold pressor and handgrip) while extracardiovascular and haemodynamic functions were assessed non-invasively at every heart beat, during baseline, stress and recovery phases. The sympathetic response was evaluated by computing the 'area-under-the-curve' (value x time) measured during the psychophysiological session. The session was repeated at run-in, after placebo and during treatment. After one month's treatment, baseline blood pressure was significantly reduced in patients treated with amlodipine (139 +/- 1/84 +/- 1 mmHg; P < 0.001) and verapamil (140 +/- 2/85 +/- 1 mmHg; P < 0.001). The emotional arousal (frontalis muscular contraction, skin conductance) was unchanged, but the cutaneous vascular response was reduced (P < 0.05) in patients treated with verapamil. No changes in systolic or diastolic blood pressure were detectable, but amlodipine increased the heart rate response (P < 0.05). In contrast, verapamil reduced the heart rate (P < 0.05) without depressing the cardiac output response, which was increased with amlodipine (P < 0.05). Total vascular resistance was significantly (P < 0.001) reduced with both the treatments. Consequently, functional cardiac load, expressed by pressure-rate product and cardiac power, was significantly enhanced with amlodipine and reduced with verapamil. In conclusion, the abnormal sympathetic stress response, which characterizes the hypertensive patient, might be affected by the choice of medication. Verapamil in particular, moderated emotional arousal, the vasoconstrictive response and reduced cardiac load without lowering cardiac output demands. In contrast, in patients treated with amlodipine, in whom the cardiac output response was increased, the pattern was reversed and the functional cardiac load was also increased.

Adult↗
PubMed1995

Changes in enzyme levels in hypertensive heart tissue.

The levels of activity of some enzymes involved in oxidative metabolism have been determined in left ventricular tissue from spontaneously hypertensive rats compared with those in normotensive controls. Levels of pyruvate kinase were increased about 1.3 fold indicative of elevated glycolytic activity. Similarly, enhanced levels of lactate dehydrogenase were found, consistent with a requirement for increased oxidation of cytosolically-generated NADH. In addition a more active malate-aspartate shuttle, which in heart provides the major route for transfer of reducing equivalents to the mitochondria, was suggested by elevated levels of the cytosolic isoenzyme of aspartate aminotransferase; malate dehydrogenase did not increase but the activity of this enzyme is very high and unlikely to be rate-limiting in the shuttle. The levels of expression of mRNAs for three of these enzymes (pyruvate kinase, aspartate aminotransferase and malate dehydrogenase) were also determined and correlated well with the extent of change, if any, in the changes in enzymatic activity. Thus it seems that one response to development of hypertension in rats is an increase in expression of the genes for certain key enzymes involved in oxidative metabolism.

Animals↗
PubMed1995

[Transcutaneous oximetry in smokers with moderate hypertension and peripheral arterial disease treated with amlodipine and defibrotide, also with total smoking cessation].

To evaluate the hemorheological influence on oxygen release after a period of 4 months of suspension from smoking and of antihypertensive treatment with amlodipine 10 mg o.d. and defibrotide 400 mg o.d. we have studied 14 smokers with II moderate hypertension (according to the World Health Organization) with hypertensive retinopathy II and slight left ventricular hypertrophy and II stage type a peripheral arterial disease according to Leriche-Fontaine classification. The total suspension for a period of 4 months from smoking associated with a Ca-antagonist such as amlodipine and an hemorheological, antithrombotic drug such as defibrotide together could bring about an improvement on the treatment of hypertension and a notable reduction in the risks linked to the complications found in hypertensives with PAOD II type a.

Amlodipine↗
PubMed1994

Controlled study with a new sustained-release formulation of nifedipine in essential hypertensive patients.

The authors studied the antihypertensive effect and tolerability of a new sustained-release formulation of nifedipine 50 mg once a day, in comparison with nifedipine retard 20 mg twice a day in patients with mild or moderate primary arterial hypertension. Both treatments significantly lowered blood pressure with no difference in daily blood pressure profile. At steady state, the two drugs determined comparable plasma levels of nifedipine as measured immediately before the morning dose. After a 12-month treatment, the new formulation of nifedipine still displayed satisfactory blood pressure control in both supine and standing positions, with no change in tolerability throughout the study. In conclusion, this new sustained-release formulation of nifedipine has similar efficacy and tolerability to conventional treatment with nifedipine retard 20 mg twice a day.

Delayed-Action Preparations↗
PubMed1994

Left-ventricular hypertrophy in the spontaneously hypertensive rat: effect of ACE inhibitors on ultrastructural morphology.

The ACE inhibitors cilazapril and captopril were administered at 10 and 100 mg/day, respectively, to spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY) from the 12th to the 22nd week of life. Both drugs produced statistically significant reductions in systolic and diastolic blood pressure, left-ventricular mass and index of left-ventricular hypertrophy in SHR. After cilazapril treatment, the morphology of SHR cardiocytes became similar to that in untreated normotensive rats, while in captopril-treated rats, myofibrils were disarranged, obliquely oriented and smaller than normal, with areas of electron-transparent sarcoplasm separating the myofibril bundles; mitochondria were also altered. In WKY rats, we observed no statistically significant changes in blood pressure, ventricular weight and hypertrophy index between the two drugs; however, there were different effects of the two drugs on the ultrastructural morphology of the myocardium. These observations suggest that these two molecularly dissimilar ACE inhibitors act differently at the tissue level despite similar effects on blood pressure and left-ventricular mass.

Animals↗
PubMed1994

Decrease of phagocytic functions in hypertensive rats.

The present investigation was aimed to examine non-specific immunologic capabilities of spontaneously hypertensive rats (SHR) during the development of hypertension. In vitro phagocytosis and oxidative killing exerted by monocytes, polymorphonuclear cells (PMN) and splenic macrophages (SpM0) were evaluated in SHR at 5-, 8-, and 24-weeks of age. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Results showed that in pre-hypertensive stage (5-wk) there was no difference between SHR and WKY rats with regard to non-specific immunologic functions. Statistically significant differences in both phagocytosis and oxidative killing arose in early hypertensive stage (8-wk) and became more marked in adult SHR with established hypertension (24-wk). In conclusion, our data provide evidence of novel immunologic abnormalities in SHR in terms of ingestion and bactericidal phagocytic capabilities. The mechanisms responsible for these impaired immunologic functions may depend on various suppressive factors which will be object of discussion.

Aging↗
PubMed1994

Diabetes modifies cardiovascular reactivity during hypertension.

Hypertension and diabetes often occur in the same patient, and this observation inspired the search for a new common pathogenetic hypothesis. The onset of diabetes during hypertension also could modify cardiovascular autonomic arousal. To identify a peculiar hemodynamic and psychophysiologic reactivity, a male population of mild essential hypertensive (166 +/- 6/102 +/- 8 mm Hg) patients (EH) and non-insulin-dependent hypertensive (169 +/- 10/101 +/- 7 mm Hg) diabetic subjects (HD) underwent a session of stress tests. Four tests, Mental Arithmetic, Incomplete Phrases, Cold Pressor, and Handgrip, were preceded and followed by a 10-minute recovery period. Functional tests were performed to identify any possible cardiac autonomic neuropathy. During the entire session, by means of a beat-to-beat noninvasive computerized device, hemodynamic and extracardiovascular functions were measured. The findings suggested the presence of a sympathetic hyperactivity in both HD and EH. In particular, HD showed a peculiar "tropism" for the peripheral vasculature. In these patients, in fact, total vascular resistance and peripheral temperature responses were 89.2% and -64.2%, respectively, versus 33.7% and -50.6%, which were found in EH. On the other hand, the ejection ventricular index was more depressed in HD (-27.9%) than in EH (-23.8%), although they did not seem to be affected by cardiac autonomic damage. The different profiles appear to confirm the increase of functional vascular damage in diabetic hypertensive patients, probably because of the insulin resistance or obsolete muscular cardiac damage.

Autonomic Nervous System↗
PubMed1994

Lipids and cardiovascular reactivity changes in hypertensive cigarette smokers: enalapril versus nifedipine treatment effects.

Cigarette smoking has many effects on the cardiovascular system, psyche, and serum lipids, which can create a vicious circle that is pejorative to the well-being of hypertensive patients, even if they are under pharmacologic treatment. To investigate the effect of two different antihypertensive agents, nifedipine and enalapril, on cardiovascular reactivity and lipoprotein patterns in cigarette smokers with hypertension, 92 essential hypertensive (175 +/- 11/103 +/- 8 mm Hg) subjects were studied, who had no sign of lipidosis, and subdivided into four groups in order of smoking habit and therapy. Over a 30-month follow-up period, the percentage changes in blood pressure (BP), heart rate (HR), triglycerides, total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were evaluated while the patients underwent a session of psychophysiologic tests to assess sympathetic reactivity. The response was calculated through the difference in cumulative percentage changes (DC%) in systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, muscular contraction (EMG), skin conductance (SCL), and peripheral temperature (TP). The office BP was reduced significantly in all groups. In the nonsmokers, enalapril reduced (p < 0.05) the SCL-, TP-, SBP-, and DBP-DC% reactivity, lowered (p < 0.05) TR, C-tot, and LDL, and increased (p < 0.05) the HDL. However, nifedipine magnified the sympathetic responses and the atherosclerotic lipoproteins and decreased (p < 0.05) the HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Stress response and antihypertensive treatment.

Results from many studies suggest that the central nervous system may play an important role in enhancing and maintaining sympathetic, metabolic and haemodynamic effects in patients with hypertension. Likewise, emotional and mental stresses may provoke phasic and sustained adrenergic responses in normotensive and untreated hypertensive patients. Because the various antihypertensive medications have different mechanisms of action, and elicit different neurovegetative responses, it is useful to distinguish between the effects of different treatments on sympathetic activity. To identify the effect of stress on sympathetic reactivity, we evaluated the extracardiovascular and haemodynamic responses to various stressor agents using noninvasive techniques. This psychophysiological approach allowed us to standardise stress, to identify individual cardioneurovegetative responses both before and during treatment, and to establish the effects of various treatments on the cardioneurovegetative response. The extracardiovascular psychophysiological response of patients with a family history of hypertension and of normotensive patients who later became hypertensive was characterised by an inability to recover after mental challenge. Therefore, prolonged sympathetic activity resulting from mental stimulation may contribute to the development of hypertension. Antihypertensive medications affected sympathetic reactivity differently. For example, nifedipine worsened sympathetic reactivity, while verapamil was able to correct abnormal neuroadrenergic responses. Furthermore, verapamil was successfully combined with enalapril in patients whose hypertension was resistant to monotherapy with the angiotensin converting enzyme (ACE) inhibitor. Therefore, the functional and structural consequences of sympathetic stimulation resulting from daily activation and pharmacological blood pressure adjustments are important in hypertensive patients, because they may have abnormal sympathetic reactivity to various stimuli.

Antihypertensive Agents↗
PubMed1993

[Clinical hemorrheology and arterial hypertension].

In order to have a good haemorheological approach to hypertensives, we have put together a review with haemorheological subjects and with the relationships between plasmatic and haematic viscosity and hypertension in relation to pathophysiology, diagnosis, prognosis and treatment. In this review we deal with: (1) Clinical haemorheology. (2) Haematic viscosity. (3) The relationship between haemorheology and hypertension and between antihypertensive drugs and haemorheology. The study of viscosity and erythrocytes deformability, and of erythrocytes and platelets stickiness could pharmacologically correct the haemorheological disorders which can be some of the causes of hypertension.

Antihypertensive Agents↗