Pulmonary elimination of angiotensin-I after experimental damage to the myocardium

Abstract

In a rat model of heart failure induced by microembolization of coronary vessels puhnonary elimination of angiotensin-I directly depends on the degree of myocardial damage, the clearance of angiotensin-I being mediated through angiotensin-conveiling enzymeindependent factors. Insufficient release of angiotensin-II from the lungs into circulation in embolized animals can be partially responsible for activation of peripheral reninangiotensin systems and aggravation of heart failure.Key Words: angiotensin-converting enzyme; lung clearance; cardiac sclerosis; heart ./ailure Activation of the renin-angiotensin system (RAS) depends on the degree of myocardial damage and the severity of heart failure [8]. Increased plasma renin activity at the late [5] and, under physical strain, early stages of heart failure [9] probably results from accelerated elimination of angiotensin-I (AT-I) in the circulation. Plasma concentrations of AT-I can remain unchanged because its production and utilization are compensated. The aim of the present study was to evaluate the relationship between the degree of myocardial damage induced by embolization of the coronary vessels and the rate of AT-I clearance. MATERIALS AND METHODSExperiments were carried out on male Wistar rats weighing 330-370 g. Coronary embolisln was induced by injecting plastic 15-g microspheres (NEN) into the left ventricle with occluded ascendant aorta [6]. Controls were sham-operated rats injected with the same volume of physiological saline via the same route. The intensity of AT-I elimination into pulmonary circulation was assessed 21 days postoperaRussian Cardiology Research-and-Production Complex, Russian Ministry of Health; M. V. Lomonosov Moscow State University tion. To this end, arterial and venous catheters werc implanted, and on the next day uSI-AT-I (14xl0 s cpm 2, 50 ng/min) was injected intravenously until attaining the equilibrium concentration. Arterial blood was sampled into the mediuna for pcptidc extraction [3]. The vortexed mixture was centrifuged, the supernatant was diluted with distilled water to 5 ml, and peptides were extracted on a Sep-pak C18 microcolumn (Waters Ass.) [211. The peptide fraction was eluted with 2 ml ethanol and dried under a nitrogen stream. Quantitative analysis of 12SI-AT-I and 12SI-AT-II was performed using high-performance liquid chromatography followed by radiometry of the corresponding nfinute eluate fractions. Puhnonary clearance was calculated as the ratio of infusion rate to blood concentration of 12SI-AT-I.For morphological analysis, the hears we re fixed in 10% neutral fornlaldehyde and elnbedded in paraffin. Microtome longitudinal sections (5-7 ~t) through the atria and ventricles were stained with hematoxylin and eosin and picrofuchsin by the van Oieson method. The following pathological phenomena were assessed: the nulnber of scars per section, focal cardiosclerosis, and cardiomyocyte hypertrophy and dystrophy. Each phenomenon was scored using a 5-point scale. The data were processed