EFFECT OF THE QUALITY OF LABORATORY RATS ON THE DYNAMICS OF PARAMETERS IN THE DEVELOPMENT OF VASORENAL HYPERTENSION IN THE “2 KIDNEYS, 1 CLAMP” MODEL

The aim of this study was to investigate the effects of the quality of laboratory rats on the dynamics of vasorenal hypertension in model “2 kidneys, 1 clamp”. Experiments were conducted on rats strain Wistar - conventional and SPF status. The dynamics of systolic blood pressure (SBP), beat-to-beat interval (RR) and components of the spectrum of heart rate variability (HRV) were explored via 1, 2 and 8 weeks after renal artery clipping. It was found, that conventional and SPF animals differ in basic parameters. SPF rats have a SBP below, RR and HRV more, compared to conventional animals. Through 8 weeks after renal artery clipping in rats with SPF status rise SBP was lower, compared to conventional animals. Marked similarities in the dynamics of vasorenal hypertension for both groups of animals: increase sympathetic nervous system activity markers of spectrum HRV in the initial weeks after renal artery clipping, stable vasorenal hypertension did not develop in all clipped rats, and the tendency to decrease the length of RR in the development of stable vasorenal hypertension. In addition, there was a significant reduction in HRV through 8 weeks following renal artery clipping in SPF rats. As a result, although vasorenal hypertension developed better in the group of conventional rats, the dynamics of variability of RR was more pronounced in animals with SPF status, besides, fewer animals with SPF status were required to detect changes in the components of the HRV spectrum than conventional animals.

Рredictors and markers of experimental vasorenal hypertension onset in the model “2 kidneys, 1 clamp”

The aimof the study was to analyze the influence of the baseline systolic blood pressure (SBP), the length of beat-to-beat interval (RR) and the components of the heart rate variability (HRV) spectrum on the development of vasorenal hypertension in the model “2 kidneys, 1 clamp” in Wistar rats. Also we investigated the relationship between anxiety and parameters of hemodynamics in intact animals using the “open field” test and the correlations between SBP level, RR duration and the components of the HRV spectrum in both intact animals and animals with renal artery ischemia.Design and methods. We recorded hemodynamic parameters on the tail of awake rats. In the HRV analysis, a low-frequency component (LF), a high-frequency component (HF) and a sympathetic-vagal balance (LF/HF) were calculated.Results. In normotensive rats the normal high SBP is accompanied by tachycardia and increased anxiety in “open field” test. The baseline values of SBP, RR interval and HRV spectrum components do not influence the development of unilateral vasorenal hypertension. In the development of unilateral vasorenal hypertension, weakened parasympathetic effects on cardiac function were observed, as evidenced by a decrease in the RR interval duration and HF component of the HRV spectrum in animals with developed hypertension, as well as an increase in the LF/HF component of HRV in clamped rats.Сonclusions. Individual increased anxiety of normotensive animals does not affect the development of vasorenal hypertension in the model “2 kidneys, 1 clamp”.

Ideas of V.Z. Golubev - freelance university lecturer of the Kazan Emperor’s university - in modern studies of renal microcirculation

In 1894 V.Z. Golubev, freelance university lecturer of the Kazan Emperor’s University, presented his thesis «Of the renal blood vessels in mammals and humans». In this work, V.Z. Golubev described the structure of two capillary networks of the renal cortex: glomerular and peritubular. He has identified true straight arterioles, false straight arterioles and direct venules of pyramids as parts of the renal medulla direct vessels. V.Z. Golubev described glomerular capillaries, located along the arcuate arteries of the kidney in the boundary layer and assigned these to the perivascular circulation, as well as noted the important role of the true direct arteriolar blood circulation to the kidneys. According to scientific researches of the second half of the XX century, the structure of the renal circulatory system is subordinated to differentiated renal blood flow in the cortex and medulla, and this is achieved by cortical and juxtamedullary blood flow. Significant increase and the duration of juxtaglomerular bypass cause severe circulatory disorders of the surface layers of kidney cortex and acute renal failure. Modern data on renal blood circulation prepared by researches of V.Z. Golubev, explain the development mechanism of various pathological conditions: acute blood loss, hydronephrosis, vasorenal hypertension, glomerulonephritis, pyelonephritis, cardiogenic shock, cardiorenal syndrome in uncontrolled coronary heart disease, arterial hypertension, sudden cardiac death etc. V.Z. Golubev created a scientific basis for further studies of renal microcirculation. The principles, outlined in his thesis, anticipated later researches of renal juxtamedullary circulation and renal circulation in healthy people and in case of a disease. The thesis of V.Z. Golubev, published 120 years ago, is still of present interest and highlights the problems requiring further research.

Cardiomyocyte apoptosis in vasorenal hypertension as a consequence of catabolism error

Aim. To investigate the effects of phosphocreatine and ethylmethylhydroxypyridine succinate on cardiomyocyte apoptosis intensity and degree of ventricular cardiomyocytes hypertrophy in rabbits with vasorenal hypertension (VH) model. Methods. VH was modeled on rabbits by artificial abdominal aortic stenosis by one-third of the diameter just above the renal arteries arising. Rabbits were divided to 4 groups: rabbits with 4-week VH without treatment, rabbits with 4-week VH treated with phosphocreatine, rabbits with 4-week VH treated with ethylmethylhydroxypyridine succinate, and healthy rabbits (control group). Cardiomyocyte apoptosis intensity and degree of ventricular cardiomyocytes hypertrophy was assessed in all of the rabbits by evaluation of nuclear-cytoplasmic ratio. Results. Use of phosphocreatine or ethylmethylhydroxypyridine succinate led to a significant reduction of the apoptotic index in the left ventricular myocardium, whereas the similar effect on the right ventricle was only typical for phosphocreatine. None of these drugs had an effect on myocardial hypertrophy degree, which remained on the same level as in the untreated hypertensive animals. Conclusions. Energy deficiency is one of the factors inducing cardiomyocyte apoptosis, so administration of phosphocreatine or ethylmethylhydroxypyridine succinate might be an important component of heart failure prevention and treatment in hypertension. Myocardial hypertrophy has no effect on the cardiomyocyte apoptosis intensity in case of proper energy supply.

BARORECEPTOR REFLEX ROLE IN BLOOD PRESSURE LONG-TERM REGULATION

Less than 50 % Wistar male rats with intact baroreceptor reflex developed arterial hypertension 8 weeks after renal artery clipping in the model «two kidneys - one clip». Blood pressure level negatively correlated with initial magnitude of the baroreceptor reflex. At the same time all rats (100 %) with the damaged baroreceptor reflex developed hypertension after renal artery clipping. Thus, we conclude that baroreceptor reflex counteracts the development of vasorenal hypertension and it can take part in blood pressure long-term regulation.

The captopril and eprosartan influence on hemodynamic parameters in rats with renovascular hypertension

The aim of this investigation is the comparison of captopril and eprosartane influence on the level blood pressure, its variability and baroreceptor reflex in normal rats and rats with vasorenal hypertension. It was shown that hypertensive rats had higher level of blood pressure, heart rate and its variability than normotensive rats. There was no relationship between arterial blood pressure and its variability in normal as well as hypertensive rats. Captopril decreased blood pressure and had no effect on variability of blood pressure. In rats with renovascular hypertension an increased baroreflex and decreased variability of heart rate was note. Eprosartan, as well as captopril, decreased blood pressure, but increased variability of blood pressure in rats with hypertension.