In 2023, six decades have elapsed since the first experimental work on the heart muscle was published, in which a member of the Institute of Physiology of the Czech Academy of Sciences participated as an author; Professor Otakar Poupa was the founder and protagonist of this research domain. Sixty years - more than half of the century - is certainly significant enough anniversary that is worth looking back and reflecting on what was achieved during sometimes very complicated periods of life. It represents the history of an entire generation of experimental cardiologists; it is possible to learn from its successes and mistakes. The objective of this review is to succinctly illuminate the scientific trajectory of an experimental cardiological department over a 60-year span, from its inaugural publication to the present. The old truth - historia magistra vitae - is still valid. Keywords: Heart, Adaptation, Development, Hypoxia, Protection.

• MeSH
• Academies and Institutes * history   MeSH
• Biomedical Research * history   trends   MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Physiology history   MeSH
• Cardiology history   trends   MeSH
• Humans MeSH
• Heart physiology   MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH

Lactacystin is a proteasome inhibitor that interferes with several factors involved in heart remodelling. The aim of this study was to investigate whether the chronic administration of lactacystin induces hypertension and heart remodelling and whether these changes can be modified by captopril or melatonin. In addition, the lactacystin-model was compared with NG-nitro-l-arginine-methyl ester (L-NAME)- and continuous light-induced hypertension. Six groups of three-month-old male Wistar rats (11 per group) were treated for six weeks as follows: control (vehicle), L-NAME (40 mg/kg/day), continuous light (24 h/day), lactacystin (5 mg/kg/day) alone, and lactacystin with captopril (100 mg/kg/day), or melatonin (10 mg/kg/day). Lactacystin treatment increased systolic blood pressure (SBP) and induced fibrosis of the left ventricle (LV), as observed in L-NAME-hypertension and continuous light-hypertension. LV weight and the cross-sectional area of the aorta were increased only in L-NAME-induced hypertension. The level of oxidative load was preserved or reduced in all three models of hypertension. Nitric oxide synthase (NOS) activity in the LV and kidney was unchanged in the lactacystin group. Nuclear factor-kappa B (NF-κB) protein expression in the LV was increased in all treated groups in the cytoplasm, however, in neither group in the nucleus. Although melatonin had no effect on SBP, only this indolamine (but not captopril) reduced the concentration of insoluble and total collagen in the LV and stimulated the NO-pathway in the lactacystin group. We conclude that chronic administration of lactacystin represents a novel model of hypertension with collagenous rebuilding of the LV, convenient for testing antihypertensive drugs or agents exerting a cardiovascular benefit beyond blood pressure reduction.

• Keywords
• captopril, fibrosis, hypertension, lactacystin, melatonin, remodelling,
• MeSH
• Acetylcysteine adverse effects   analogs & derivatives   MeSH
• Antihypertensive Agents administration & dosage   pharmacology   MeSH
• Fibrosis MeSH
• Hypertension chemically induced   drug therapy   etiology   MeSH
• Captopril administration & dosage   pharmacology   MeSH
• Rats MeSH
• Melatonin administration & dosage   pharmacology   MeSH
• Disease Models, Animal MeSH
• NG-Nitroarginine Methyl Ester adverse effects   MeSH
• Rats, Wistar MeSH
• Ventricular Remodeling drug effects   MeSH
• Heart Ventricles drug effects   pathology   MeSH
• Light adverse effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Acetylcysteine MeSH
• Antihypertensive Agents MeSH
• Captopril MeSH
• lactacystin MeSH Browser
• Melatonin MeSH
• NG-Nitroarginine Methyl Ester MeSH

Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day) exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group) were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day) or melatonin (10 mg/kg/day). Exposure to continuous light led to hypertension, left ventricular (LV) hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

• MeSH
• Antihypertensive Agents therapeutic use   MeSH
• Hypertension drug therapy   MeSH
• Angiotensin-Converting Enzyme Inhibitors therapeutic use   MeSH
• Captopril therapeutic use   MeSH
• Blood Pressure drug effects   MeSH
• Rats MeSH
• Melatonin therapeutic use   MeSH
• Oxidative Stress drug effects   MeSH
• Rats, Wistar MeSH
• Light * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antihypertensive Agents MeSH
• Angiotensin-Converting Enzyme Inhibitors MeSH
• Captopril MeSH
• Melatonin MeSH

The aim of the study was to find out whether the changes in nutritional status induced by different litter size during early postnatal development can influence quantitative and qualitative protein remodeling and contractile performance of the myocardium. Male Wistar rats born at the same day were pooled together at 2 days postbirth and assigned by random selection to dams in groups of 4, 8 or 16 rats/litter. The animals were investigated at the age of 4 and 16 weeks. The results revealed that the early postnatal nutritional modification altered weight parameters: whereas lower heart weight persisted in slow-growing rats until 16 weeks, higher body weight of fast-growing rats returned to the control level at the age of 16 weeks. Altered nutritional status influenced also protein remodeling of the myocardium: the concentration of all noncollagenous proteins (fractions of metabolic and contractile proteins) significantly increased in slow-growing rats, on the other hand, the concentration of collagenous proteins (pepsin-soluble and -insoluble fractions) was higher in fast-growing animals. The changes were, however, only transitional: three months after the end of the weaning period most protein changes returned to the control level. However, higher concentration of total blood lipids and triglycerides in fast-growing rats persisted until adulthood. Nutritional changes had, however, only minor effect on ventricular performance. No differences among groups were observed in basal values of the left ventricular pressure, while the maximum pressure attained after an acute ventricular loading and the contractile reserve were significantly decreased in slow-growing 4 week old rats. The functional consequence of altered nutritional status during weaning was only transitional, in agreement with the transient character of most structural and biochemical markers of myocardial remodeling.

• MeSH
• Ventricular Function, Left MeSH
• Heart Function Tests MeSH
• Animal Nutritional Physiological Phenomena MeSH
• Animals, Suckling MeSH
• Myocardial Contraction MeSH
• Blood Glucose metabolism   MeSH
• Rats MeSH
• Myocardium metabolism   MeSH
• Nutritional Status * MeSH
• Weaning * MeSH
• Rats, Wistar MeSH
• Proteins metabolism   MeSH
• Heart physiology   MeSH
• Body Weight MeSH
• Organ Size MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Blood Glucose MeSH
• Proteins MeSH

The effect of chronic administration of beta-guanidinopropionic acid (GPA) on the protein profiling, energy metabolism and right ventricular (RV) function was studied in the rat heart during the weaning and adolescence period. GPA was given in tap water (1-1.5%) using pair drink controls. The feeding of animals with GPA solution for a six week period resulted in elevation of heart to body weight ratio due to body growth retardation. GPA accumulated in the myocardium up to 67.37 +/- 5.3 mumoles.g dry weight and the tissue content of total creatine, phosphocreatine and ATP was significantly decreased to 15%, 9% and 65% of control values respectively. Total activity of creatine kinase (CK) was not changed, but the proportion of mitochondrial (Mi) CK isoenzyme was decreased; the percentage of MB isoenzyme of CK was significantly higher. GPA treatment resulted in an elevation of the content of cardiac collagenous proteins and decrease of non-collagenous proteins in the heart; in parallel, a decrease of the collagen I to collagen III ratio was detected. The function of the RV was assessed using an isolated perfused heart with RV performing pressure-volume work. As compared to pair-drink controls, RV function was significantly impaired the GPA group: at any given right atrial filling pressure, the RV systolic pressure and the rate of pressure development were decreased by almost a factor of two. Elevation of the RV diastolic pressure with increasing pulmonary artery diastolic pressure was also significantly steeper in the GPA group which also showed decrease of cardiac output, especially at high outflow resistance. It may be assumed that chronic administration of GPA deeply influenced metabolic parameters, protein profiles and contractile function of the developing heart. On the other hand, concentrations of glucose, total lipids and triglycerides in blood plasma were not affected. All these data confirm the concept that the CK system is of central importance both for heart function and for the regulation of normal growth of cardiac myocytes.

• MeSH
• Phosphocreatine deficiency   MeSH
• Guanidines pharmacology   MeSH
• Isoenzymes MeSH
• Coronary Circulation MeSH
• Creatine Kinase metabolism   MeSH
• Blood Pressure MeSH
• Rats MeSH
• Myocardium metabolism   MeSH
• Carbon Monoxide metabolism   MeSH
• Rats, Wistar MeSH
• Propionates pharmacology   MeSH
• Sarcoplasmic Reticulum drug effects   metabolism   MeSH
• Heart drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Phosphocreatine MeSH
• guanidinopropionic acid MeSH Browser
• Guanidines MeSH
• Isoenzymes MeSH
• Creatine Kinase MeSH
• Carbon Monoxide MeSH
• Propionates MeSH