Jana Matuskova

Regression of left ventricular hypertrophy and aortic remodelling in NO‐deficient hypertensive rats: effect of l‐arginine and spironolactone

Aim:  We investigated, whether the substrate for nitric oxide (NO) formation –l‐arginine – and the aldosterone receptor antagonist – spironolactone – are able to reverse alterations of the left ventricle (LV) and aorta in Nω‐nitro‐l‐arginine methyl ester (l‐NAME)‐induced hypertension.

Impaired Endothelial Function of Thoracic Aorta in Hereditary Hypertriglyceridemic Rats

Abstract: Objective—Hereditary hypertriglyceridemia (hHTG) in rats was found to be associated with metabolic abnormalities and elevation of blood pressure. There is controversy regarding the relation between hHTG and vascular function. The aim of this study was to determine the reactivity and accompanying structural changes in thoracic aorta from hereditary hypertriglyceridemic rats and hHTG rats that were given, for a long time, NG‐nitro‐l‐arginine methyl ester (L‐NAME) with and without simultaneous captopril treatment. Methods—Isolated rings of thoracic aorta were mounted in organ chambers for isometric tension recording or for measurement of endothelium‐dependent relaxation. Morphological changes of thoracic aorta (wall thickness, diameter) were measured using light microscopy. Results—Endothelium‐dependent relaxation (EDR) to acetylcholine (ACh, 10−5 M) was significantly attenuated in the hHTG group compared to control Wistar rats (59.3 ± 8.5% vs. 95.8 ± 6.5%, p < 0.001), but normalized after pretreatment with captopril. EDR to ACh was further inhibited in hHTG rats treated with L‐NAME (36.0 ± 2.3%, p < 0.001). Maximum residual relaxation was only partly restored with captopril treatment (72.4 ± 5.8%, p < 0.001). Hypertriglyceridemia did not significantly alter the sensitivity of the thoracic aorta to exogenous noradrenaline. The diameter/wall thickness (D/W) ratio in aortas of control Wistar rats averaged 16.25 ± 0.57. This ratio was significantly lower in hHTG rats (12.52 ± 0.38, p < 0.01) and was not altered after treatment with captopril. In the hHTG rats treated with L‐NAME, the D/W ratio was further significantly decreased (8.25 ± 0.30, p < 0.001). Simultaneous captopril treatment attenuated the decrement of this ratio (9.80 ± 0.75, p < 0.05). Conclusions—Results showed that hHTG is accompanied by functional and morphological alterations in the rat thoracic aorta. These changes in hHTG and in hHTG rats treated with L‐NAME could be, at least in part, protected by captopril treatment.

Heart remodeling in the hereditary hypertriglyceridemic rat: effect of captopril and nitric oxide deficiency.

Abstract: Aim—The hereditary hypertriglyceridemic (hHTg) rat is characterized by insulin resistance, hypertension, and hypertriglyceridemia. Thus, we investigated whether (a) remodeling of the heart left ventricle (LV) is present under the given hypertensive situation and (b) whether this potential alteration could be influenced by an inhibition of the angiotensin converting enzyme (ACE) and/or by a blockade of nitric oxide production. Methods—Five groups of rats were investigated: control Wistar (C) rats, hHTg rats, hHTg rats given captopril (100 mg/kg/day) (hHTg + CAP) or NG‐nitro‐l‐arginine methyl ester (L‐NAME, 40 mg/kg/day) (hHTg + L‐NAME), and hHTg rats given the combination of both drugs (hHTg + CAP + L‐NAME) for 28 days. Systolic blood pressure (SBP) was measured by tail‐cuff plethysmography each week. After cervical dislocation, the relative weights of the left and right ventricles (LV/BW, RV/BW) were obtained, the LV nucleic acid concentrations were analyzed, and the fibrosis amount was quantified with aid of a semiquantitative histological technique. Results—In the hHTg group, the increased SBP (141.7 ± 4.4 vs. 117.2 ± 3.1 mmHg in controls) was linked to hypertrophy of the LV (1.63 ± 0.05 vs. 1.30 ± 0.03 g/kg in controls) with only a minimum of fibrosis. DNA concentration in the LV was decreased (0.45 ± 0.03 vs. 0.69 ± 0.04 mg/g w.w. in controls) in the hHTg group. Captopril normalized SBP and decreased the LV/BW (1.44 ± 0.04 g/kg). Chronic administration of L‐NAME to the hHTg rats additionally enhanced (189.3 ± 5.9 mmHg) the already raised SBP, stimulated fibrosis development, and increased DNA concentration (0.54 ± 0.02 mg/g w.w.) in the LV compared to hHTg group, yet without additional weight increase of the LV. The combined treatment of the hHTg rats with CAP and L‐NAME resulted in normal SBP and the development of LV hypertrophy, and fibrosis was substantially reduced. Conclusions—(a) The heart of hHTg rats carries signs of LV hypertrophy with minimal fibrosis. (b) Nevertheless, LV fibrosis was increased in the hHTg + L‐NAME group. (c) Captopril normalized SBP and decreased the extent of LV hypertrophy in both the nontreated hHTg and the hHTg + L‐NAME groups and (d) substantially reduced the development of LV fibrosis in the hHTg + L‐NAME group. LVH in hHTg rats may be induced by sympathoadrenal system activation, circulating volume enlargement, and impairment of nitric oxide (NO) production rather than by activation of the renin‐angiotensin‐aldosterone system.

Effects of captopril, spironolactone, and simvastatin on the cardiovascular system of non-diseased Wistar rats

a Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic b 3rd Clinic of Internal Medicine, School of Medicine, Comenius University, Bratislava, Slovak Republic c Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic d Center of Excellence NOREG, Slovak Republic e Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic f Department of Medical Biochemistry, 2nd School of Medicine, Charles University, Prague, Czech Republic g Department of Physiology, School of Medicine, Charles University, Hradec Kralove, Czech Republic

PROTEIN REMODELING OF THE HEART VENTRICLES IN HEREDITARY HYPERTRIGLYCERIDEMIC RAT: EFFECT OF ACE-INHIBITION

The aim of this study was to determine whether protein remodeling of the heart ventricles and remodeling of the aorta were present in hereditary hypertriglyceridemic (hHTG) rats and whether treatment with the angiotensin-converting enzyme inhibitor, captopril could prevent these alterations. Three groups of rats were investigated in a four week experiment control Wistar /C/rats, hHTg rats, hHTg rats given captopril (100 mg/kg/day) (hHTg + CAP). In the hHTg group, the increased systolic blood pressure (SBP) was associated with hypertrophy of the LV and RV. Protein profile analysis revealed an enhancement of metabolic protein concentration in both ventricles. The concentration of total collagenous proteins was not changed in either ventricles. However, alterations in composition of cardiac collagen were detected, characterized by higher concentration of hydroxyproline in pepsin-insoluble fraction and lower concentration of hydroxyproline in pepsin soluble faction in the LV. Hypertrophy of aorta, associated with the reduction of nitric oxide dependent relaxation, was also present in hHTG rats. Captopril normalized SBP, reduced left ventricular hypertrophy (LVH), diminished metabolic protein concentration in both ventricles, and improved NO-dependent relaxation of the aorta. Furthermore, captopril partially reversed alterations in hydroxyproline concentration in soluble and insoluble collagenous fractions of the LV. We conclude that hypertrophy of both ventricles and the aorta are present in hHTG rats, along with protein remodeling of both ventricles. Captopril partially prevented left ventricular hypertrophy development and protein remodeling of the myocardium.