L-name-induced Hypertension Does Not Completely Reproduce The Hemodynamic Pattern Of The Hypertensive-diabetic Cardiomyopathy In Rats

Renovascular hypertension (2K1C) + type 1 diabetes mimics the morphological abnormalities described in the cardiomyopathy induced by L-NAME in rats, but their hemodynamic patterns are still controversial. The present study investigated the cardiovascular function in these two models of cardiomyopathy in rats after 8 weeks of treatment. Wistar rats were divided into the following groups: Control (C); L-NAME (L)-60 mg/kg/ day; 2K1C+DM (R+D)-streptozotocin (60 mg/kg) and one renal artery clipped. The following parameters were measured: mean arterial pressure (MAP), heart rate, cardiac output (CO) and total peripheral vascular resistance (TPVR). dP/dt+ and dP/dt- were also evaluated in an isolated heart setup. L and R+D groups had increased MAP (175.4±29.7 and 158.7±16.7 mmHg, respectively) and reduced CO after the 8th week. TPVR was increased in both groups. A decrease in dP/dt+ was found in the R+D (1895±98 mmHg/s, p<0.05) vs. C group (2534±120 mmHg/ s, p< 0.05). dP/dt- was diminished in the L and R+D groups vs. C group (1490±104 and 1460±94 mmHg/s, respectively vs. 2080±92 mmHg/s, p<0.05). Our study indicates that the hemodynamic abnormalities found in R+D and L-induced cardiomyopathies are not quite similar as well as their previously described histopathological features.314449Moncada, S., Palmer, R.M., Higgs, E.A., Nitric oxide: Physiology, pathophysiology, and pharmacology (1991) Pharmacol Rev, 43 (2), pp. 109-142. , Jun;Arnal, J.F., el Amrani, A.I., Chatellier, G., Menard, J., Michel, J.B., Cardiac weight in hypertension induced by nitric oxide synthase blockade (1993) Hypertension, 22 (3), pp. 380-387. , Sep;Moreno Júnior, H., Metze, K., Zatz, R., De Nucci, G., Chronic nitric oxide blockade causes cardiac ischaemia but not cardiac hypertrophy: An experiment of four weeks in rats (1994) Verh Dtsch Ges Path, 78, p. 459Pechánová, O., Bernátová, I., Effect of long-term NO synthase inhibition on cyclic nucleotide content in rat tissues (1996) Physiol Res, 45 (4), pp. 305-309Babál, P., Pechánová, O., Bernátová, I., Stvrtina, S., Chronic inhibition of NO synthesis produces myocardial fibrosis and arterial media hyperplasia (1997) Histol Histopathol, 12 (3), pp. 623-629. , Jul;Bernátová, I., Pechánová, O., Kristek, F., Mechanism of structural remodelling of the rat aorta during long-term NG-nitro-L-arginine methyl ester treatment (1999) Jpn J Pharmacol, 81 (1), pp. 99-106. , Sep;Pechánová, O., Bernátová, I., Babál, P., Structural alterations in the heart after long-term L-NAME and D-NAME treatment (1999) Gen Physiol Biophys, 18 (SUPPL. 1), pp. 6-9. , Dec;Lip, G.Y., Felmeden, D.C., Li-Saw-Hee, F.L., Beevers, D.G., Hypertensive heart disease. A complex syndrome or a hypertensive 'cardiomyopathy'? (2000) Eur Heart J, 21 (20), pp. 1653-1665. , Oct;Grossman, E., Messerli, F.H., Diabetic and hypertensive heart disease (1996) Ann Intern Med, 125 (4), pp. 304-310. , Aug 15;Sowers, J.R., Epstein, M., Frohlich, E.D., Diabetes, hypertension, and cardiovascular disease: An update (2001) Hypertension, 37 (4), pp. 1053-1059. , Apr;Factor, S.M., Minase, T., Cho, S., Capasso, J.M., Sonnenblick, E.H., Coronary microvascular abnormalities in the hypertensive-diabetic rat. A primary cause of cardiomyopathy? (1984) Am J Pathol, 116 (1), pp. 9-20. , Jul;Mathis, D.R., Liu, S.S., Rodrigues, B.B., McNeill, J.H., Effect of hypertension on the development of diabetic cardiomyopathy (2000) Can J Physiol Pharmacol, 78 (10), pp. 791-798. , Oct;Kojda, G., Harrison, D., Interactions between NO and reactive oxygen species: Pathophysiological importance in atherosclerosis, hypertension, diabetes and heart failure (1999) Cardiovasc Res, 43 (3), pp. 562-571. , Aug 15;Bayraktutan, U., Yang, Z.K., Shah, A.M., Selective dysregulation of nitric oxide synthase type 3 in cardiac myocytes but not coronary microvascular endothelial cells of spontaneously hypertensive rat (1998) Cardiovasc Res, 38 (3), pp. 719-726. , Jun;Hink, U., Li, H., Mollnau, H., Oelze, M., Matheis, E., Hartmann, M., Skatchkov, M., Munzel, T., Mechanisms underlying endothelial dysfunction in diabetes mellitus (2001) Circ Res, 88 (2), pp. E14-E22. , Feb 2;Sampaio, R.C., Tanus-Santos, J.E., Melo, S.E., Hyslop, S., Franchini, K.G., Luca, I.M., Moreno Jr, H., Hypertension plus diabetes mimics the cardiomyopathy induced by nitric oxide inhibition in rats (2002) Chest, 122 (4), pp. 1412-1420. , Oct;Goldblatt, H., Lynch, J., Hanzal, R.F., Summerville, W.W., Studies on experimental hypertension. The production of persistent elevation of systolic blood pressure by means of renal ischemia (1934) J Exp Med, 59, pp. 347-379Moreno Jr, H., Metze, K., Antunes, E., Zatz, R., De Nucci, G., Chronic nitric oxide inhibition as a model of hypertensive heart muscle disease (1996) Basic Res Cardiol, 91 (3), pp. 248-255. , May-Jun;Zatz, R., A low cost tail-cuff method for the estimation of mean arterial pressure in conscious rats (1990) Lab Anim Sci, 40 (2), pp. 198-201. , Mar;Langendorff, Untersuchungen am überlebenden Säugethierherzen. (1895) Pflügers Arch Ges Physiol, pp. 291-332Sigmon, D., Beierwaltes, W.H., Influence of nitric oxide in the chronic phase of two-kidney, one clip renovascular hypertension (1998) Hypertension, 31 (2), pp. 649-656. , Feb;Zhong, N., Zhang, Y., Zhu, H.F., Wang, J.C., Fang, Q.Z., Zhou, Z.N., Myocardial capillary angiogenesis and coronary flow in ischemia tolerance rat by adaptation to intermittent high altitude hypoxia (2002) Acta Pharmacol Sin, 23 (4), pp. 305-310. , Apr;Fredersdorf, S., Thumann, C., Ulucan, C., Griese, D.P., Luchner, A., Riegger, G.A., Kromer, E.P., Weil, J., Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats (2004) Cardiovasc Pathol, 13 (1), pp. 11-19. , Jan-Feb;Sun, Y., Zhang, J., Lu, L., Bedigian, M.P., Robinson, A.D., Weber, K.T., Tissue angiotensin II in the regulation of inflammatory and fibrogenic components of repair in the rat heart (2004) J Lab Clin Med, 143 (1), pp. 41-51. , Jan;Matsubara, B.B., Matsubara, L.S., Zornoff, L.A., Franco, M., Janicki, J.S., Left ventricular adaptation to chronic pressure overload induced by inhibition of nitric oxide synthase in rats (1998) Basic Res Cardiol, 93 (3), pp. 173-181. , Jun;Pessanha, M.G., Mandarim-de-Lacerda, C.A., Influence of the chronic nitric oxide synthesis inhibition on cardiomyocytes number (2000) Virchows Arch, 437 (6), pp. 667-674. , Dec;Maejima, Y., Adachi, S., Ito, H., Nobori, K., Tamamori-Adachi, M., Isobe, M., Nitric oxide inhibits ischemia/reperfusion-induced myocardial apoptosis by modulating cyclin A-associated kinase activity (2003) Cardiovasc Res, 59 (2), pp. 308-320. , Aug 1;Pechánová, O., Bernátová, I., Pelouch, V., Babál, P., L-NAME-induced protein remodeling and fibrosis in the rat heart (1999) Physiol Res, 48 (5), pp. 353-362Stockklauser-Färber, K., Ballhausen, T., Laufer, A., Rösen, P., Influence of diabetes on cardiac nitric oxide synthase expression and activity (2000) Biochim Biophys Acta, 1535 (1), pp. 10-20. , Dec 15;Bojunga, J., Dresar-Mayert, B., Usadel, K.H., Kusterer, K., Zeuzem, S., Antioxidative treatment reverses imbalances of nitric oxide synthase isoform expression and attenuates tissue-cGMP activation in diabetic rats (2004) Biochem Biophys Res Commun, 316 (3), pp. 771-780. , Apr 9;Moshage, H., Nitric oxide determinations: Much ado about NO.-thing? (1997) Clin Chem, 43 (4), pp. 553-556. , Apr;Jungersten, L., Edlund, A., Petersson, A.S., Wennmalm, A., Plasma nitrate as an index of nitric oxide formation in man: Analyses of kinetics and confounding factors (1996) Clin Physiol, 16 (4), pp. 369-379. , Jul;Kobayashi, T., Kamata, K., Effect of chronic insulin treatment on NO production and endothelium-dependent relaxation in aortae from established STZ-induced diabetic rats (2001) Atherosclerosis, 155 (2), pp. 313-320. , Apr;Andrew, P.J., Mayer, B., Enzymatic function of nitric oxide synthases (1999) Cardiovasc Res, 43 (3), pp. 521-531. , Aug 15;Cai, H., Harrison, D.G., Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress (2000) Circ Res, 87 (10), pp. 840-844. , Nov 10;Koo, J.R., Vaziri, N.D., Effects of diabetes, insulin and antioxidants on NO synthase abundance and NO interaction with reactive oxygen species (2003) Kidney Int, 63 (1), pp. 195-201. , Jan