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Role of lymphatics in development of experimental vasorenal hypertension
DETERMINANT ROLE OF ANGIOTENSIN AT, RECEPTORS IN THE PATHOGENESIS OF INSULIN-INDUCED HYPERTENSION IN RATS Wann-Chu Huang and Te-Chao Fang* Graduate Institute of Medical Sciences, Tzu Chi College of Medicine and Department of Internal Medicine, Tzu Chi General Hospital *, Hualien, Tuiwan, Republic qf China
ROLE OF LYMPHATICS IN DEVELOPMENT OF EXPERIMENTAL VASORENAL HYPERTENSION L. E. Bulekbaeva, M. R. Khanturin, G. A. Demchenko, N. A. Akhmetbaeva Institute of Human and Animals Physiology of Academy of Sciences, Almaty, Republic Kazakhstan Contractile activity and adrenergic innervation of lymphatics were studied under experimental vasorenal hypertension. A model of vasorenal hypertension was obtained by unilateral nephrectomy and the ligation of the contrlateral kidney. The rats were applied 1% solution of NaCl for the drink and the injection of desoxycorticosteron -acetat. Adrenergic innervation of lymphatics wall was studied under fluorescent microscope. Diffusion of catecholamine from adrenergic fibers into lymphatics wall and destruction of fibers in the vessel wall were founded in hypertensive rats. The spontaneous contractile activity of the isolated lymphatics in hypertensive rats were diminished at 2-3 time, than in normotensive rats. Effect of adrenaline on the contractile reaction of isolated lymphatics in hypertensive rats increased. Blocking of aadrenoreceptors of the lymphatic smooth muscle cells by pirroxan shown that the activity of adrenal system elevated in hypertension. Effects of acetylcholine and histamine on the lymphatic contraction were diminished as compared with the control experiments. Thus, under vasorenal hypertension, adrenergic innervation of lymphatics is attenuated, the contractility of lymphatics is changed.
Experiments were conducted to evaluate the effects of angiotensin subtype 1 (AT,) and 2 (AT]) receptor antagonists (losartan and PD1233 19, respectively) on blood pressure (BP) in chronic hyperinsulinemia-induced hypertension in rats. Sustained insulin infusion (21 pmol/kg.min) via subcutaneous osmotic minipump significantly increased systolic BP from 139*3 to 151&l and 157+2 mmHg after 4 and 6 weeks of insulin infusion. The plasma insulin concentration increased by 2-3 times but no significant changes in the plasma glucose and triglycerides concentrations were noted. The hypertensive rats exhibited insulin resistance. Combined losartan (3.5 pg/kg.min) and insulin infusion prevented the rise of blood pressure and improved insulin resistance. When hypertension had established, superimposed infusion of losartan, but not PD1233 19 (1 .O pgkg.min), on insulin significantly reduced BP. Combined treatment of losartan and PD123319 did not affect the antihypertensive effect of losartan in insulin-infused rats. These results indicate that angiotensin ATI receptors play a determinant role in the pathogenesis of hyperinsulinemia-induced hypertension in the rat.
MYOCARDIAL HYPERTROPHY IN RABBITS WITH RENOVASCULAR HYPERTENSION AFTER BLOCK OF ANGIOTENSIN SYSTEM V. Frolov, G. Drozdova, V. Mustyatsa, V. Balayev Russian Peoples ’ Department of Pathophysiologv, Friendship University, Moscow, Russia
RENAL XANTHINE OXIDOREDUCTASE ACTIVITY IN EXPERIMENTAL HYPERTENSION Juha Laakso’, Eero Mervaala’, Terttu-Liisa Teravainen’ and Risto Lapatto2.3 Institute of Biomedicine, Departments of ‘Medical Chemistry, and ‘Pharmacology and Toxicology, P.O. Box 8. FIN-00014 University of Helsinki, Finland; ‘Helsinki University Hospital for Children and Adolescents, FIN00029 HUCH, Finland
Peculiarities of hypertrophied myocardium involution under effects of lotensin (ACE inhibitor) and valsartan (angiotensin II receptor antagonist) were studied in rabbits with renovascular arterial hypertension (AH). Myocardium of left ventricle was investigated by means of optic and electronic microscopy 14 weeks after AH modulation. According to experimental data both preparations caused significant decrease in blood pressure (BP) and weight of myocardium (3.44&0.06g in untreated animals; 2.00+0.07g in group treated with lotensin; 1.88+0.04g in group treated with valsartan) with no correlation between extents of such a decrease in both parameters. Morphological analysis showed that in treated animals on the background of myocardial weight reduction the interrelation of its similar to that of remains structural elements hypertrophied myocardium (decrease in number of capillaries and mitochondria pro myocardial mass unit, extension of collagen). So possibly reduction of heart weight after block of angiotensin system could be caused not by BP reduction but through direct effect of preparations on cardiac metabolism. Moreover block of angiotensin results in myocardial weight reduction with remained signs of hypertrophy.
Clinical and experimental studies have established an association between high sodium intake and arterial hypertension. Sodium-induced experimental hypertension is associated with increased renal mass by mechanisms, which are not fully worked out. In the present study we demonstrate an increased kidney xanthine oxidoreductase (XOR) activity in two models of essential hypertension (spontaneously hypertensive and Dahl salt-sensitive rats). Increased sodium intake produced a dose-dependent kidney XOR activity increase only in the salt-sensitive rats. XOR is induced by hypoxia and catalyses the formation of urate, an antioxidant, from ATP degradation products hypoxanthine and xanthine. These findings may be important in delineating the mechanisms behind salt sensitivity and the pathogenesis of arterial hypertension.
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ROLE OF LYMPHATICS IN DEVELOPMENT OF EXPERIMENTAL VASORENAL HYPERTENSION L. E. Bulekbaeva, M. R. Khanturin, G. A. Demchenko, N. A. Akhmetbaeva Institute of Human and Animals Physiology of Academy of Sciences, Almaty, Republic Kazakhstan Contractile activity and adrenergic innervation of lymphatics were studied under experimental vasorenal hypertension. A model of vasorenal hypertension was obtained by unilateral nephrectomy and the ligation of the contrlateral kidney. The rats were applied 1% solution of NaCl for the drink and the injection of desoxycorticosteron -acetat. Adrenergic innervation of lymphatics wall was studied under fluorescent microscope. Diffusion of catecholamine from adrenergic fibers into lymphatics wall and destruction of fibers in the vessel wall were founded in hypertensive rats. The spontaneous contractile activity of the isolated lymphatics in hypertensive rats were diminished at 2-3 time, than in normotensive rats. Effect of adrenaline on the contractile reaction of isolated lymphatics in hypertensive rats increased. Blocking of aadrenoreceptors of the lymphatic smooth muscle cells by pirroxan shown that the activity of adrenal system elevated in hypertension. Effects of acetylcholine and histamine on the lymphatic contraction were diminished as compared with the control experiments. Thus, under vasorenal hypertension, adrenergic innervation of lymphatics is attenuated, the contractility of lymphatics is changed.
Experiments were conducted to evaluate the effects of angiotensin subtype 1 (AT,) and 2 (AT]) receptor antagonists (losartan and PD1233 19, respectively) on blood pressure (BP) in chronic hyperinsulinemia-induced hypertension in rats. Sustained insulin infusion (21 pmol/kg.min) via subcutaneous osmotic minipump significantly increased systolic BP from 139*3 to 151&l and 157+2 mmHg after 4 and 6 weeks of insulin infusion. The plasma insulin concentration increased by 2-3 times but no significant changes in the plasma glucose and triglycerides concentrations were noted. The hypertensive rats exhibited insulin resistance. Combined losartan (3.5 pg/kg.min) and insulin infusion prevented the rise of blood pressure and improved insulin resistance. When hypertension had established, superimposed infusion of losartan, but not PD1233 19 (1 .O pgkg.min), on insulin significantly reduced BP. Combined treatment of losartan and PD123319 did not affect the antihypertensive effect of losartan in insulin-infused rats. These results indicate that angiotensin ATI receptors play a determinant role in the pathogenesis of hyperinsulinemia-induced hypertension in the rat.
MYOCARDIAL HYPERTROPHY IN RABBITS WITH RENOVASCULAR HYPERTENSION AFTER BLOCK OF ANGIOTENSIN SYSTEM V. Frolov, G. Drozdova, V. Mustyatsa, V. Balayev Russian Peoples ’ Department of Pathophysiologv, Friendship University, Moscow, Russia
RENAL XANTHINE OXIDOREDUCTASE ACTIVITY IN EXPERIMENTAL HYPERTENSION Juha Laakso’, Eero Mervaala’, Terttu-Liisa Teravainen’ and Risto Lapatto2.3 Institute of Biomedicine, Departments of ‘Medical Chemistry, and ‘Pharmacology and Toxicology, P.O. Box 8. FIN-00014 University of Helsinki, Finland; ‘Helsinki University Hospital for Children and Adolescents, FIN00029 HUCH, Finland
Peculiarities of hypertrophied myocardium involution under effects of lotensin (ACE inhibitor) and valsartan (angiotensin II receptor antagonist) were studied in rabbits with renovascular arterial hypertension (AH). Myocardium of left ventricle was investigated by means of optic and electronic microscopy 14 weeks after AH modulation. According to experimental data both preparations caused significant decrease in blood pressure (BP) and weight of myocardium (3.44&0.06g in untreated animals; 2.00+0.07g in group treated with lotensin; 1.88+0.04g in group treated with valsartan) with no correlation between extents of such a decrease in both parameters. Morphological analysis showed that in treated animals on the background of myocardial weight reduction the interrelation of its similar to that of remains structural elements hypertrophied myocardium (decrease in number of capillaries and mitochondria pro myocardial mass unit, extension of collagen). So possibly reduction of heart weight after block of angiotensin system could be caused not by BP reduction but through direct effect of preparations on cardiac metabolism. Moreover block of angiotensin results in myocardial weight reduction with remained signs of hypertrophy.
Clinical and experimental studies have established an association between high sodium intake and arterial hypertension. Sodium-induced experimental hypertension is associated with increased renal mass by mechanisms, which are not fully worked out. In the present study we demonstrate an increased kidney xanthine oxidoreductase (XOR) activity in two models of essential hypertension (spontaneously hypertensive and Dahl salt-sensitive rats). Increased sodium intake produced a dose-dependent kidney XOR activity increase only in the salt-sensitive rats. XOR is induced by hypoxia and catalyses the formation of urate, an antioxidant, from ATP degradation products hypoxanthine and xanthine. These findings may be important in delineating the mechanisms behind salt sensitivity and the pathogenesis of arterial hypertension.
54