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2.
Scand J Med Sci Sports ; 25(3): 382-9, 2015 Jun.
Article in English | MEDLINE | ID: mdl-24766540

ABSTRACT

Adult and adolescent elite black athletes display - as compared with their white counterparts - excessively increased left ventricle (LV) wall thickness (LVWT), mass (LVM), and relative wall thickness (RWT). To investigate such ethnicity-related differences in non-professional adolescent athletes, 138 male, amateur football players [age 14.0 ± 1.7 years, 42 West-African blacks (BA) and 96 Italian whites (WA)] underwent an echocardiographic study of LV diameters, LVWT, maximal wall thickness (MWT), LVM, and RWT as remodeling index. BA vs WA exhibited greater thickness of septum and posterior wall, higher MWT (10.3 ± 1.7 vs 8.8 ± 1.1 mm), and higher LVM (117 ± 27 vs 101 ± 20 g/m(2)) and RWT (0.44 ± 0.07 vs 0.35 ± 0.04). Age, systolic blood pressure, body mass index, and ethnicity predicted MWT and LVM, whereas ethnicity was the sole strong predictor of RWT. The greater MWT, LVWT, and LVM of 14-year-old, amateur-level BA vs WA indicates that ethnicity substantially affects LV structure in adolescent, non-professional athletes. In contrast with MWT and LVM, elevated RWT was predicted by black ethnicity only. We suggest that concentric-type LV remodeling is a peculiar LV phenotype in adolescent African athletes.


Subject(s)
Adaptation, Physiological , Athletes , Black People , Heart Ventricles/diagnostic imaging , Soccer , Ventricular Remodeling , White People , Adolescent , Africa, Western/ethnology , Blood Pressure , Body Mass Index , Child , Echocardiography , Humans , Italy , Male , Organ Size
3.
Ital Heart J ; 2(1): 49-54, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11214702

ABSTRACT

BACKGROUND: It is well known that sexual hormones, in particular estrogens, may influence the cardiovascular system. Experimental and clinical studies have shown that estrogen directly or indirectly modulates the reactivity of vascular smooth muscle but at present the mechanism of action of this hormone has yet to be clarified. The aim of this study was to evaluate the vascular effects of a synthetic non-steroid estrogen, diethylstilbestrol, and the possible involvement of endothelial function. METHODS: We investigated, on aortic strips of a female rabbit, the inhibitory effects of diethylstilbestrol on the contractions induced by different spasmogenic agents, noradrenaline (10(-6) M), angiotensin II (10(-6) M), serotonin (10(-6) M), and KCl (10(-1) M). Some experiments were performed in high K+, Ca++-free solution. In some experiments endothelial function was abolished by mechanical ablation. Another series of experiments was incubated (30 min) with N(G)-monomethyl-L-arginine, which inhibits nitric oxide synthase or with tamoxifen, a specific antagonist of estrogen receptors. RESULTS: At doses from 10(-6) M to 10(-4) M, diethylstilbestrol showed an evident spasmolytic action on contractions induced by noradrenaline, angiotensin II and serotonin but no significant effect was observed on KCl spasm. The inhibitory response of diethylstilbestrol to increased vascular tone induced by noradrenaline disappeared when the endothelial function, validated by the acetylcholine test, was abolished by mechanical ablation. When tested in high K+, Ca++-free solution, diethylstilbestrol did not significantly shift the cumulative dose-response curve of calcium. In the experiments performed with N(G)-monomethyl-L-arginine, diethylstilbestrol failed to induce vasodilation suggesting that its action may be related to synthesis of nitric oxide. Moreover, in the presence of tamoxifen, diethylstilbestrol was unable to induce vasodilation. CONCLUSIONS: The early occurrence of vasodilation is in favor of a direct effect and seems to exclude a regulation of gene expression. These results suggest that estrogens may directly regulate vascular tone interacting with its specific endothelial cell receptors through the release of nitric oxide.


Subject(s)
Diethylstilbestrol/pharmacology , Endothelium, Vascular/drug effects , Estrogens, Non-Steroidal/pharmacology , Vasodilator Agents/pharmacology , Animals , Aorta/physiology , Dose-Response Relationship, Drug , Endothelium, Vascular/physiology , Female , Rabbits , Receptors, Estrogen/physiology
4.
Eur J Echocardiogr ; 2(2): 108-17, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11882437

ABSTRACT

AIMS: Doppler tissue echocardiography (DTE) was applied to extract the myocardial wall velocities along different planes and evaluate the left ventricular function in essential hypertension. METHODS AND RESULTS: Fifty-four hypertensives (HT) were compared to a control group of 31 normotensive (NT) subjects. The short-axis shortening and lengthening was assessed through the parasternal projections, sampling from interventricular septum and posterior wall. Through the apical projections the mitral annulus excursion was observed at four sites (anterior, posteroseptal, lateral, inferior walls) to assess the longitudinal dynamic of the heart. In each myocardial segment, peak velocity and time-velocity integral for systolic (S) and diastolic waves (E and A) were measured and their means for the long- and short-axis directions were calculated. Significant changes in hypertensives involved mainly the longitudinal motion. In diastole, the E-wave relaxation velocity was significantly decreased and the late A-wave velocity was unchanged. The E/A velocity ratio was significantly reduced. Relaxation velocity was negatively correlated to age, left ventricular mass and diastolic blood pressure. In systole, the peak S-wave shortening velocity was reduced and no association with age, left ventricular mass and blood pressure could be demonstrated. The range of segmental data produced by DTE proved useful to manufacture sensitive indices for recognition of hypertensive damage. Single DTE variables also proved slightly more sensitive than those extracted from the mitral flow pattern for the discrimination of HT patients. CONCLUSION: The presence of impaired relaxation was confirmed by DTE in a large portion of patients with hypertension and left ventricular hypertrophy. A peculiar systolic disturbance is evidenced by this technique. DTE-derived information can be used to detect early and quantify target-organ damage and its progression or regression during antihypertensive treatment.


Subject(s)
Echocardiography, Doppler , Adult , Age Factors , Aged , Antihypertensive Agents/therapeutic use , Blood Flow Velocity/physiology , Blood Pressure/drug effects , Female , Follow-Up Studies , Heart Septum/diagnostic imaging , Heart Ventricles/diagnostic imaging , Humans , Hypertension/diagnostic imaging , Hypertension/drug therapy , Hypertension/physiopathology , Italy/epidemiology , Male , Middle Aged , Myocardial Contraction/physiology , Regression Analysis , Statistics as Topic , Stroke Volume/physiology , Ventricular Function, Left/physiology
6.
Rev Soc Bras Med Trop ; 31(5): 465-72, 1998.
Article in Portuguese | MEDLINE | ID: mdl-9789445

ABSTRACT

Renal anatomopathological lesions were studied among 119 AIDS patients from Faculdade de Medicina do Triângulo Mineiro's University Hospital (Uberaba, MG, Brazil). From formalin-fixed blocks, slides were obtained and studied by light microscopy. Of 119 patients, 67 presented tubulointerstitial nephritis (TIN), 18 inespecific, 2 xantogranulomatous and infections agents were found in 48 as follows: mycosis in 28 (16 Cryptococcus sp; 9 Histoplasma sp, 1 Candida sp e 2 Paracoccidioides brasiliensis); bacteria in 18 (9 Mycobacterium sp), virus in 6 (Cytomegalovirus). Acute tubular necrosis was found in 43 cases (36.1%). Other diagnosis were: nefrocalcinosis (15.1%), arteriolar hyalinosis (22.7%), two cases of focal segmental glomerulosclerosis (1.7%) and one case of diffuse mesangial hyperplasia (0.8%). We conclude that the renal involvement in patients with AIDS, presents a wide spectrum of pathologies, secondary to complications related to opportunistic infections, therapeutic and diagnostic management, and the nephropathies associated to HIV.


Subject(s)
Acquired Immunodeficiency Syndrome/pathology , Kidney/pathology , AIDS-Related Opportunistic Infections/pathology , Adolescent , Adult , Autopsy , Female , Humans , Male , Middle Aged
7.
Rev. Soc. Bras. Med. Trop ; 31(5): 465-472, set.-out. 1998. tab, ilus
Article in Portuguese | LILACS | ID: lil-463602

ABSTRACT

Renal anatomopathological lesions were studied among 119 AIDS patients from Faculdade de Medicina do Triângulo Mineiro's University Hospital (Uberaba, MG, Brazil). From formalin-fixed blocks, slides were obtained and studied by light microscopy. Of 119 patients, 67 presented tubulointerstitial nephritis (TIN), 18 inespecific, 2 xantogranulomatous and infections agents were found in 48 as follows: mycosis in 28 (16 Cryptococcus sp; 9 Histoplasma sp, 1 Candida sp e 2 Paracoccidioides brasiliensis); bacteria in 18 (9 Mycobacterium sp), virus in 6 (Cytomegalovirus). Acute tubular necrosis was found in 43 cases (36.1%). Other diagnosis were: nefrocalcinosis (15.1%), arteriolar hyalinosis (22.7%), two cases of focal segmental glomerulosclerosis (1.7%) and one case of diffuse mesangial hyperplasia (0.8%). We conclude that the renal involvement in patients with AIDS, presents a wide spectrum of pathologies, secondary to complications related to opportunistic infections, therapeutic and diagnostic management, and the nephropathies associated to HIV.


As alterações anatomopatológicas renais foram estudadas em 119 casos de indivíduos com a síndrome da imunodeficiência humana adquirida (SIDA) no Hospital Escola da Faculdade de Medicina do Triângulo Mineiro, Uberaba MG. A partir das amostras de rim fixadas em formol, foram confeccionadas lâminas e analisadas ao microscópio de luz. Dos 119 casos estudados, 67 tiveram diagnóstico de nefrite túbulo intersticial (NTI), sendo 18 inespecíficas, 2 xantogranulomatosas e encontrou-se agente infeccioso em 48: fungos em 28 (16 Cryptococcus sp, 9 Histoplasma sp, 1 Candida sp e 2 Paracoccidioides brasiliensis); bactérias em 18 (9 Mycobacterium sp); vírus em 6, Citomegalovírus. Em 43 havia necrose tubular aguda (NTA). Outros diagnósticos foram: nefrocalcinose (15,1%) e hialinose arteriolar (22,7%). Encontrou-se também 2 casos com glomeruloesclerose segmentar focal (GESF) e um caso de hiperplasia mesangial difusa. Houve predomínio da NTI, que pode ser devido às infecções oportunistas, predominando as fúngicas; a toxicidade por drogas ou ainda devido a possível ação direta do próprio vírus. A necrose tubular aguda (NTA), foi a segunda causa em freqüência, de acometimento renal da amostra. Concluiu-se que o envolvimento renal nos pacientes com SIDA apresenta um espectro variado de processos patológicos, principalmente relacionados com infecções oportunistas, o tratamento e os procedimentos para diagnósticos, e ainda as nefropatias associadas ao vírus da imunodeficiência humana (VIH).


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Kidney/pathology , Acquired Immunodeficiency Syndrome/pathology , Autopsy , AIDS-Related Opportunistic Infections/pathology
8.
Cardiology ; 88(4): 315-22, 1997.
Article in English | MEDLINE | ID: mdl-9197424

ABSTRACT

We studied 21 patients undergoing valve replacement for severe aortic stenosis and marked left ventricular dysfunction (mean ejection fraction 27 +/- 7.9%) without significant coronary disease or other valve diseases. At 5-60 months (average 26 +/- 18) after surgery, the patients underwent a clinical history, physical examination and a complete M-mode, two-dimensional and Doppler transthoracic echocardiographic study. Thirteen patients were examined with cardiopulmonary exercise testing. Two patients with a low preoperative transvalvular pressure gradient (<50 mm Hg) died postoperatively. Nineteen patients were tested at follow-up. All patients showed an improvement in functional class, an increase in ejection fraction (EF), a normalization in left ventricular diameters, volumes and stress indices and a reduction in left ventricular mass which correlated with EF increase. Cardiopulmonary exercise testing showed a good exercise capacity. In conclusion, in patients affected by severe aortic stenosis and marked preoperative left ventricular dysfunction valve replacement induces a favorable remodeling of the left ventricle, as shown by a late postoperative examination. The regression of hypertrophy is a positive event which correlates with the improvement in EF.


Subject(s)
Aortic Valve Stenosis/surgery , Heart Valve Prosthesis , Heart Ventricles/diagnostic imaging , Stroke Volume/physiology , Ventricular Dysfunction, Left/physiopathology , Aged , Aged, 80 and over , Aortic Valve , Aortic Valve Stenosis/complications , Aortic Valve Stenosis/diagnostic imaging , Echocardiography, Doppler , Exercise Test , Female , Follow-Up Studies , Heart Ventricles/physiopathology , Humans , Hypertrophy, Left Ventricular/complications , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/physiopathology , Male , Middle Aged , Prognosis , Retrospective Studies , Time Factors , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology
9.
Recenti Prog Med ; 88(6): 255-63, 1997 Jun.
Article in Italian | MEDLINE | ID: mdl-9289761

ABSTRACT

The finding of normocholesterolaemia, characterized by plasmatic values of total cholesterol < 2 g/l, which may hide silent lipidic alterations, is not by itself sufficient to rule out the existence of cardiovascular risk. First level screening of patients exposed to atherogenic risk must begin from dosage of three basic lipidic indicators, represented by total cholesterol, triglycerides, and HDL cholesterol. By using the values of the three above-mentioned indicators and by applying Friedewald's formula, it is possible to calculate LDL cholesterol indirectly. Atherogenic risk is present when HDL cholesterol and LDL cholesterol show plasmatic concentration inferior to 0.35 g/l and superior to 1,3 g/l respectively. The European Atherosclerosis Society lists five hyperlipidaemic classes, from A to E, determined on the basis of plasmatic levels of cholesterol and triglycerides. Mild hypercolesterolaemia associated with modest atherogenic risk and which largely occurs in people and is frequently underestimated form a diagnostic point of view, contributes to cardiovascular mortality more considerably than more serious forms of hypercholesterolaemia. On the basis of this observation, there originated the programmatic proposal for the prevention of hyperlipidaemic complications, presented by the Authors.


Subject(s)
Hypercholesterolemia/classification , Hypercholesterolemia/diagnosis , Arteriosclerosis/etiology , Arteriosclerosis/mortality , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Medical History Taking , Obesity/blood , Physical Examination , Prognosis , Risk , Severity of Illness Index , Surveys and Questionnaires
10.
J Cardiovasc Pharmacol ; 29(4): 463-70, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9156355

ABSTRACT

We investigated the effects of human calcitonin gene-related peptide (CGRP) on isolated rabbit hearts to evaluate the mechanisms responsible for the vasodilatory action of the peptide on the coronary district, monitoring contemporaneously the effects on left ventricular pressure (LVP) and heart rate (HR). We also evaluated the reactivity of the human internal mammary artery (IMA) to excitatory drugs acting with different mechanisms and the inhibitory response to CGRP in comparison with the commonly used vasodilatory agents. The peptide induced a slight inhibitory effect on the basal coronary perfusion pressure (CPP), whereas it was ineffective on the inotropism and chronotropism. A more detectable coronary vasodilation was evident when CPP was increased by spasmogenic agents [vasopressin, methoxamine, Bay K 8644, and prostaglandin F2 alpha (PGF2 alpha)]. This inhibitory effect was dose dependent (10(-11)-10(-8) M) and apparently not specific, occurring to the same extent on different stimuli. Forskolin (10(-8) M), an adenylate-cyclase activator, and indomethacin (1.4 x 10(-5) M), a cyclooxygenase inhibitor, did not modify the spasmolytic activity of CGRP on precontracted coronary smooth muscle. The experiments performed on the segments of IMA, used for myocardial revascularization of patients affected by coronary diseases, have shown an evident spasmolytic action of CGRP on increased vascular tone induced by KCl (90 mM), noradrenaline (10(-5) M), serotonin (10(-6) M), and angiotensin II (10(-6) M). These inhibitory responses of CGRP on the spasmogenic compounds disappeared when the endothelial function of IMA, validated by the acetylcholine test, was abolished by mechanical ablation. A series of IMA segments was incubated (30 min) with N(G)-monomethil-L-arginine (L-NMMA), which inhibits nitric oxide (NO) synthase. In these experiments, the peptide failed to induce the vasodilation, suggesting that its action may be related to synthesis of NO. All these results show that CGRP is able to induce a potent vasodilatory action on different vessels of humans (internal mammary artery) and animals (rabbit coronary arteries). In particular the data obtained from IMA demonstrated that the vasorelaxant effect was related to synthesis of NO, one of the most studied endothelium-derived relaxing factors (EDRFs).


Subject(s)
Calcitonin Gene-Related Peptide/pharmacology , Heart/drug effects , Mammary Arteries/drug effects , Muscle, Smooth, Vascular/drug effects , Vasodilator Agents/pharmacology , Adult , Aged , Animals , Blood Pressure/drug effects , Calcitonin Gene-Related Peptide/physiology , Calcium Channel Agonists/pharmacology , Coronary Vessels/drug effects , Cyclooxygenase Inhibitors/pharmacology , Dose-Response Relationship, Drug , Female , Heart Rate/drug effects , Humans , Male , Middle Aged , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/physiology , Myocardial Contraction/drug effects , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/antagonists & inhibitors , Rabbits , Vasoconstrictor Agents/pharmacology , omega-N-Methylarginine/pharmacology
11.
Gen Pharmacol ; 27(7): 1255-9, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8981077

ABSTRACT

1. The calcium-channel blocking activity of lacidipine has been studied compared with that of nifedipine and verapamil on the isolated rabbit heart and aorta. 2. All the compounds induced a dose-dependent negative inotropic effect (10(-8)-10(-5) M); although lacidipine showed less, but longer lasting, activity. 3. Lacidipine showed a weak negative chronotropic effect and nifedipine was ineffective. Only verapamil strongly decreased the heart rate. 4. The three calcium antagonists abolished vasopressin-induced coronary spasm and inhibited partially metoxamine-induced coronary spasm. Only lacidipine reduced basal coronary pressure. 5. In the aortic strips, all the compounds antagonized KCl-induced contractions, and they exerted a partial effect on noradrenaline- and angiotensin II-induced contractions.


Subject(s)
Calcium Channel Blockers/pharmacology , Dihydropyridines/pharmacology , Animals , Aorta, Thoracic/drug effects , Coronary Circulation/drug effects , Female , Heart/drug effects , Heart Rate/drug effects , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Myocardial Contraction/drug effects , Nifedipine/pharmacology , Rabbits , Ventricular Pressure/drug effects , Verapamil/pharmacology
13.
Cardiologia ; 37(9): 607-13, 1992 Sep.
Article in Italian | MEDLINE | ID: mdl-1292864

ABSTRACT

We have studied retrospectively 106 patients aged 69 years or older (range 69 to 79) who underwent cardiac surgery between November 1986 and December 1989. The majority of patients (61%) were male. Coronary artery bypass surgery was performed in 59 patients, isolated valve replacement in 38 and combined valve replacement with coronary artery bypass surgery in 5. Two patients underwent ascending aorta replacement for aortic dissection and 2 ventricular aneurysmectomy and postinfarction ventricular septal defect repair. The mean postoperative hospital stay was 12 days. Ninety-one percent of patients underwent a primary elective operation and 9% required an emergency operation. Hospital mortality was 5% (n = 6). All hospital survivors were followed up by telephone contact (mean follow-up: 37 months) to determine presence or absence of chest pain, dyspnea, postoperative NYHA class and the overall effect of surgery on quality of life. There were 16 follow-up deaths; 5 were non cardiac. Follow-up study showed significant improvement in symptom status and quality of life (96%). We concluded that cardiac surgery in the elderly, although associated with increased operative risk, gives excellent relief of symptoms and good survival.


Subject(s)
Cardiac Surgical Procedures , Aged , Cardiac Surgical Procedures/mortality , Cardiac Surgical Procedures/statistics & numerical data , Cause of Death , Chi-Square Distribution , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Postoperative Complications/epidemiology , Postoperative Complications/mortality , Quality of Life , Retrospective Studies , Survival Analysis , Time Factors
14.
Cardiologia ; 36(9): 729-34, 1991 Sep.
Article in Italian | MEDLINE | ID: mdl-1686991

ABSTRACT

We compared the effects of the phosphodiesterase inhibitor amrinone, the beta-adrenergic partial agonist xamoterol and the digitalis glycoside, ouabain, on isolated rabbit hearts perfused with the Langendorff technique. Heart rate, left ventricular pressure, as an index of myocardial contractility and coronary perfusion pressure, as an index of coronary resistances, were assessed before and after each drug. Perfusion with concentrations of each agent varying from 10(-9) to 10(-4) M induced a dose-dependent increase of left ventricular systolic pressure averaging 32.5 +/- 1.5% after amrinone (10(-5) M), 46.2 +/- 0.5% after xamoterol (10(-5) M) and 19.0 +/- 2.1% after ouabain (10(-4) M). Among the 3 agents, only amrinone was able to reduce basal coronary perfusion pressure (18.4 +/- 1.2% at the dose of 10(-5) M) and inhibit vasopressin-induced coronary spasm (86.8 +/- 2.5% inhibition at 10(-5) M); no significant change of coronary perfusion pressure was noted with either xamoterol or ouabain. Heart rate was not significantly modified by amrinone whereas, at the doses of 10(-5)-10(-4) M, xamoterol increased it by 21.6 +/- 0.7% and ouabain reduced it by 12.3 +/- 1.1%. Our results show that amrinone, in comparison with digitalis glycosides and beta-adrenergic agonists, presents the unique property to increase myocardial contractility with concomitant coronary vasodilation without significant changes of heart rate. Ouabain has a less potent positive inotropic activity and a slight negative chronotropic action, whereas xamoterol inotropic effect is accompanied by an increase of heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Amrinone/pharmacology , Cardiotonic Agents/pharmacology , Coronary Vessels/drug effects , Heart Rate/drug effects , Myocardial Contraction/drug effects , Adrenergic beta-Agonists/pharmacology , Animals , In Vitro Techniques , Ouabain/pharmacology , Propanolamines/pharmacology , Rabbits , Vasodilation/drug effects , Xamoterol
15.
Pharmacol Res ; 24(2): 163-74, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1749746

ABSTRACT

The effects of captopril and of other angiotensin-converting enzyme inhibitors (zofenopril, fosenopril and enalaprilic acid) were tested on the isolated rabbit heart and aorta. Captopril elicited an erratic negative inotropic effect and a reduction in basal coronary perfusion pressure (10(-5)-10(-4) M). The increase of coronary perfusion pressure induced by vasopressin, methoxamine, angiotensin II and Bay K 8644 was partially antagonized by captopril (10(-7)-10(-4) M) in a non-specific manner. These actions were not modified by saralasin or indomethacin and by ex vivo pretreatment with captopril itself. On the aortic strips, the contraction plateau induced by KCl and angiotensin II was partially inhibited (10(-6)-10(-4) M), while no effect was observed on those induced by noradrenaline, serotonin and PGF2 alpha. The Ca2+ concentration-response curve appeared shifted to the right in a non-competitive manner. The other angiotensin-converting enzyme inhibitors showed no effect up to 10(-4) M on isolated heart or aorta. Results obtained with captopril were consistent with vasorelaxant activity independent of the tissue renin-angiotensin system. Modulatory activity on the intracellular calcium movement may be involved.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Captopril/pharmacology , Hemodynamics/drug effects , Animals , Aorta, Thoracic/drug effects , Blood Pressure/drug effects , Coronary Circulation/drug effects , Female , Heart Rate/drug effects , In Vitro Techniques , Male , Muscle Contraction/drug effects , Rabbits
16.
J Cardiovasc Pharmacol ; 16(5): 839-46, 1990 Nov.
Article in English | MEDLINE | ID: mdl-1703609

ABSTRACT

Recent reports suggested that a complex alteration in beta-receptor function occurs in failing human myocardium. We evaluated beta-receptor-subtype activity in an experimental model of monocrotaline (MCT)-induced cardiomyopathy in the rat. Through pulmonary hypertension, MCT causes right ventricular hypertrophy (RVH), either associated with heart failure or not, beta-Receptor function was evaluated in both failing-hypertrophic and hypertrophic hearts in binding studies with [125I]iodocyanopindolol (ICYP) and by measuring adenylate cyclase (AC) activity. In the right failing ventricle, beta 1- but not beta 2-receptor density was decreased. Lesion-associated modifications in the adenylate cyclase system were also observed: isoproterenol- and guanosine 5' [beta, gamma-imido]triphosphate [Gpp(NH)p]-stimulated cyclic AMP formation was reduced in the right failing ventricle, while the cyclic AMP responses to NaF and forskolin were unchanged. On the other hand, no changes in either beta-receptor density or function were found in hypertrophic ventricles. MCT-induced heart failure in the rat is thus associated with a selective decrease of beta 1-receptor density and function. These results suggest that MCT-induced cardiac failure may be an appropriate model in which to investigate heart insufficiency further.


Subject(s)
Cardiac Output, Low/physiopathology , Receptors, Adrenergic, beta/physiology , Adenylyl Cyclases/analysis , Animals , Autoradiography , Cardiomegaly/physiopathology , Cardiomyopathies/chemically induced , Cardiomyopathies/physiopathology , Female , GTP-Binding Proteins/physiology , Guanylyl Imidodiphosphate/pharmacology , Iodocyanopindolol , Monocrotaline , Pindolol/analogs & derivatives , Pindolol/metabolism , Pyrrolizidine Alkaloids , Rats , Rats, Inbred Strains , Receptors, Adrenergic, beta/analysis
17.
Cardiologia ; 35(7): 543-50, 1990 Jul.
Article in Italian | MEDLINE | ID: mdl-1965156

ABSTRACT

Reports in the literature have suggested that a complex alteration in beta-receptor pathway takes place in failing human myocardium. The purpose of our study was to evaluate the beta-adrenergic receptor system in an experimental model of heart failure induced by monocrotaline in rats. Monocrotaline, administered with a single intraperitoneal injection (50 mg/Kg), causes pulmonary hypertension and right ventricular hypertrophy, associated with congestive heart failure. beta 1 and beta 2-receptors were characterized in the right ventricle by direct radioligand binding utilizing [125I] Iodocyanopindolol and selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists. Adenylate cyclase was measured in basal condition and in the presence of different stimulators as isoproterenol with ICI 118551 (beta 1-receptor-stimulated activity), isoproterenol with CGP 20712A (beta 2-receptor-stimulated activity), Gpp(NH)p, NaF and forskolin. In the right ventricle of the failing hearts the beta 1-receptor density decreased selectively (-55.8%) while the beta 2-receptor density was unchanged. Modifications in the adenylate cyclase system were demonstrated: a reduction in the basal and beta 1- and beta 2-stimulated adenylate cyclase activity; a decrease in adenylate cyclase activation elicited by Gpp(NH)p, but not by forskolin and NaF. In conclusion, these data suggest that in monocrotaline-induced heart failure in the rat there is a selective beta 1-receptor down-regulation and an impaired coupling efficiency of G proteins. These results are in line with biochemical changes found in patients with heart failure.


Subject(s)
Heart Failure/physiopathology , Receptors, Adrenergic, beta/physiology , Adenylyl Cyclases/metabolism , Animals , Female , Heart Failure/enzymology , Rats
18.
Cardiologia ; 34(5): 431-7, 1989 May.
Article in Italian | MEDLINE | ID: mdl-2569360

ABSTRACT

The aim of this study concerned the pharmacological investigation of the isolated internal mammary artery. Spirally-cut vascular segments were obtained from patients undergoing myocardial revascularization and set up in isolated baths under isometrical tension. Reactivity of internal mammary artery preparations to stimulatory and inhibitory agents was evaluated. KCl (90 mM), noradrenaline (10-8)-10(-5) M) and serotonine (10(-9)-10(-5) M) induced a tonic contraction lasting for more than 60 min. Angiotensin II (10(-6)-10(-5) M) and dopamine (10)-8)-10(4) M) resulted virtually uneffective. The serotonine-induced contractions were strongly inhibited by ketanserin (10-9)-10(-6) M), a selective S2-blocker, and also by verapamil (10(-3)-10(-6) M) and nitroglycerin (10(-7)-10(-5) M). These data suggest that internal mammary artery is sensitive to different contractile agents, in particular serotonine activates muscular contractions through S2 receptors. The knowledge of such a mechanism may be of clinical relevance.


Subject(s)
Mammary Arteries/drug effects , Thoracic Arteries/drug effects , Vasomotor System/drug effects , Acetylcholine/pharmacology , Adult , Aged , Angiotensin II/pharmacology , Dopamine/pharmacology , Humans , Male , Middle Aged , Myocardial Revascularization , Norepinephrine/pharmacology , Potassium Chloride/pharmacology , Serotonin/pharmacology
19.
Pharmacology ; 38(3): 185-90, 1989.
Article in English | MEDLINE | ID: mdl-2471217

ABSTRACT

Steroid sex hormones, testosterone, progesterone and diethylstilbestrol, have been tested on the isolated rabbit heart. These hormones produced a negative inotropic effect (1-10 mumol/l) and an inhibitory effect on the vasopressin- or ergonovine-induced coronary spasm (0.1-10 mumol/l). Basal coronary tone was increased by testosterone and progesterone, while diethylstilbestrol induced a slight reduction of coronary perfusion pressure. The negative inotropic effect was reversed by calcium and isoprenaline, thus resembling the calcium entry blocker activity. The activation of myocardial and coronary contractility by the calcium agonist, Bay K 8644, was antagonized by all these hormones. These observations demonstrated an influence of steroid sex hormones with calcium fluxes in the isolated rabbit heart.


Subject(s)
Gonadal Steroid Hormones/pharmacology , Heart/drug effects , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology , Animals , Coronary Circulation/drug effects , Diethylstilbestrol/pharmacology , Female , Heart Rate/drug effects , In Vitro Techniques , Male , Progesterone/pharmacology , Rabbits , Testosterone/pharmacology
20.
Gen Pharmacol ; 20(3): 313-7, 1989.
Article in English | MEDLINE | ID: mdl-2744397

ABSTRACT

1. The inhibitory actions of amiodarone on the isolated rabbit heart and aorta have been studied. 2. Amiodarone inhibited vasopressin- and ergonovine-induced coronary spasm, starting from a concentration of 10(-7) M which did not affect myocardial contractility to 10(-4) M, which decreased myocardial contractility. 3. Sinus node activity was largely unaffected even when the highest dose of 10(-4) M was used. 4. Amiodarone did not modify the smooth muscle contraction in rabbit aorta strips precontracted with noradrenaline or potassium. 5. Comparison with other inhibitors of the cardiovascular system (alpha- and beta-blockers, nitrates, calcium entry blockers) points out a peculiar pharmacological profile of amiodarone and indicates some doubts about its presumed anti-adrenergic properties.


Subject(s)
Amiodarone/pharmacology , Heart/drug effects , Muscle, Smooth, Vascular/drug effects , Animals , Aorta, Thoracic/drug effects , Blood Pressure/drug effects , Coronary Circulation/drug effects , Drug Interactions , Female , Heart Rate/drug effects , In Vitro Techniques , Male , Muscle Contraction/drug effects , Myocardial Contraction/drug effects , Rabbits
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