The effect of the angiotensin converting enzyme (ACE) inhibitor, captopril, on proteosynthesis in the aorta, acetylcholine-stimulated aortic relaxation and endothelaemia (circulating endothelial cells) was investigated in rabbits with aortic insufficiency. The animals were studied 28 days after experimental intervention. Cardiac volume overload stimulated proteosynthesis in the aorta as reflected by increased ribonucleic acid (RNA) concentration and [14C] leucine incorporation into proteins of the aorta. Moreover, the number of endothelial cells in the blood was increased. The administration of captopril starting from the second day of the haemodynamic overload, partially prevented the increase both in aortic proteosynthesis and in endothelaemia. Despite these alterations, the relaxing ability of the aorta to acetylcholine was not changed either by the haemodynamic overload or by captopril. We conclude that the increase of proteosynthesis in the aorta and of endothelaemia in the early period of chronic cardiac volume overload in rabbits were partially prevented by chronic captopril treatment. Neither aortic insufficiency nor captopril changed the acetylcholine-induced relaxation of the aorta.
The aim of the study was to assess whether angiotensin converting enzyme (ACE) inhibition with captopril prevents the development of hypertension and myocardial hypertrophy and affects nitric oxide synthase (NOS) activity in rats. Animals were divided into five groups: control, two groups receiving NG-nitro-L-arginine methyl ester (L-NAME) 20 or 40 mg/kg/day, a group receiving captopril 100 mg/kg/day and a group concomitantly treated with 40 mg/kg/day L-NAME plus 100 mg/kg/day captopril. After four weeks, systolic blood pressure (SBP) significantly increased in both L-NAME groups by 30 % and 34 %, respectively. In the captopril group, SBP significantly decreased by 30 % and in the captopril plus L-NAME group SBP was not changed as compared to the controL Although left ventricular weight/body weight (LVW/BW) ratio in both L-NAME groups was significantly elevated by 19 % and 29 %, respectively, no alterations in LVW/BW ratio were found in the captopril group and captopril plus L-NAME group. In both groups receiving L-NAME, NOS activity significantly decreased by 17 % and 69 % in the heart, by 14 % and 26 % in the aorta, by 60 % and 73 % in the brain and by 13 % and 30 % in the kidney, respectively. Captopril did not influence NO synthase activity in any of the studied tissues. We conclude that captopril prevents the development of hypertension and LV hypertrophy without affecting NO formation.
We investigated the effect of captopril on the growth of the left ventricle in an experimental model of aortic insufficiency. Four groups of rabbits were studied 28 days after experimental intervention: 1. control, 2. control with captopril (10 mg/kg/day), 3. aortic insufficiency, 4. aortic insufficiency with captopril (10 mg/kg/day). Aortic insufficiency induced hypertrophic growth of the left ventricle demonstrated by increased weight and ribonucleic acid (RNA) concentration. Administration of captopril only slightly attenuated the weight increase of the left ventricle and the increase in concentration of left ventricular RNA. However, captopril reduced the concentration of left ventricular deoxyribonucleic acid (DNA) both in the control and even more in the group with aortic insufficiency. The chronic haemodynamic overload enhanced mitochondrial respiration in the left ventricle which was not influenced by captopril. We conclude that captopril in the dose 10 mg/kg/day did not prevent hypertrophy of the left ventricle but reduced left ventricular DNA concentration.
Hypertriglyceridemia and hypertension seem to be very important cardiovascular risk factors. The Prague hereditary hypertriglyceridemic (hHTG) rat was developed as a model of human hypertriglyceridemia. It was demonstrated that these rats are not obese, they are hypertensive and insulin resistant and they have some disturbances in glucose
metabolism. Several QTLs were identified for blood pressure, its particular components (dependent on major vasoactive systems) and plasma triglycerides throughout the genome of hHTG rats by using of F2 hybrids strategy. It is evident that hHTG rats are a suitable model for the study of metabolic disturbances in relation to blood pressure as well as for the
search of genetic determinants of these abnormalities. Numerous abnormalities of blood pressure regulation as well as alterations in the structure and function of cardiovascular apparatus (heart, conduit and resistance arteries) were found in hHTG rats. A special attention was paid to possible changes in the efficiency of various vasoactive systems such as
nitric oxide, renin-angiotensin-aldosterone system and sympathetic nervous system, which seem to contribute substantially to cardiovascular and/or metabolic abnormalities observed in Prague hereditary hypertriglyceridemic rats.
Hypertrophy of the left heart ventricle as a consequence of a haemodynamic overload is a process of ambiguous biological value. Although hypertrophy allows to increase the performance of the ventricle without substantial elevation in wall tension, it represents a risk factor of cardiac morbidity and mortality. The regression of hypertrophy seems to be a rational outcome of this ambivalent situation. Mot every reversal of hypertrophied muscle mass, however, can be unambiguously considered therapeutic success. The biological value of hypertrophy regression depends on the type of hypertrophy, on the level of deterioration of the heart by a long- lasting haemodynamic overload, as well as on the way in which the reversal of hypertrophy is achieved. Even in the case when functional characteristics are preserved or even improved compared to the hypertrophied heart, hypertrophy regression need not automatically mean a decrease of the cardiovascular risk induced by ventricular hypertrophy. Regression of hypertrophy may be even disadvantageous in those situations when reduction of hypertrophy and reduction of the haemodynamic overload proceed in a disproportional manner. Spontaneously developing regression of the hypertrophied left ventricle as demonstrated on the model of aortal insufficiency, is an explicitly pathological state, resulting in heart failure. Regression of myocardial hypertrophy should not be considered the primary therapeutic aim but rather a part of the management of haemodynamic overload of the heart. The main aim is to achieve optimal perfusion of the periphery, yet at the same time to provide such conditions which would prevent the working load of the heart to become a limiting factor of survival.