Effects of L-NAME, DEXA and L-NAME+DEXA on Systemic Blood Pressure of Hypertensive Pregnant and Non-Pregnant Wistar albino Rats

Yıl 2018, Cilt: 2 Sayı: 3, 78 - 85, 31.12.2018

Muharrem Balkaya , Gülsüm Bacak

https://doi.org/10.30704/http-www-jivs-net.460833

Cited By: 1

Öz

Objective: NO-inhibition has no effect on blood pressure (BP) of some spontaneous hypertensive animals, but when combined with dexamethasone (DEXA), it increases BP. The study compared effects of L-NAME and/or DEXA on systemic BP of spontaneously hypertensive pregnant and non-pregnant Wistar albino rats. Method: In two simultaneous experiments 62 female rats were used. All animals were mated for 7 days. Sperm positive (n1 = 33) and negative (n2 = 29) animals were each divided randomly into 4 groups. BPs were recorded in both experiments on the 15^th day from tails indirectly, and then animals were given Physiologic Saline (Controls), L-NAME (150mg/kg/day), DEXA (100µg/kgBW/day) or L-NAME+DEXA (150mg and 100-µg per kg BW/day) for consequent 5 days. At 19^th day, BPs were measured again, before applications. Then, animals put into individual metabolic cages for 24-h urine collection. Thereafter, blood was collected under ether anesthesia, animals were euthanized and necropsied. Weights of animals (BWs), left kidneys, adrenal glands, and fetuses; food consumptions; 24-h urine volume; urinary proteins, blood glucose, and fetus numbers were determined. Data were analyzed by ANOVA and ANOVA for repeated measures. Results: In pregnant animals, L-NAME had higher BWs than DEXA and L-NAME+DEXA (P = 0.021 and P = 0.012, respectively). In non-pregnant animals, DEXA reduced BWs significantly compared with controls (P=0.042). Interventions influenced only the diastolic blood pressure of pregnant animals (P = 0.043). The difference between DEXA and L-NAME+DEXA was significant (P = 0.044). The effects of interventions on other variables varied according to whether animals are pregnant or not. Conclusion: L-NAME and/or DEXA did not influence BP in hypertensive rats. 

Anahtar Kelimeler

Wistar albino rats, L-NAME, dexamethasone

Kaynakça

• Adeagbo AS, Triggle CR. (1993). Interactions of nitric oxide synthase inhibitors and dexamethasone with alpha-adrenoceptor-mediated responses in rat aorta. British Journal of Pharmacology, 109(2), 495–501.
• Baker M, Rahman T, Hall D, Avery PJ, Mayosi BM, Cornell JM, Farall M, Watkins H, Keavney B. (2007). The C-532T polymorphism of the angiotensinogen gene is associated with pulse pressure: a possible explanation for heterogeneity in genetic association studies of AGT and hypertension. International Jornal of Epidemiology, 36(6), 1356–1362.
• Beatty WW, Scouten CW, Beatty PA. (1971). Differential effects of dexamethasone and body weight loss on two measures of activity. Physiology and Behavior, 7(6), 869–871.Bernatova I. (2014). Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence? BioMed Research International, 2014:598271. doi: 10.1155/2014/598271.
• Calver A, Collier J, Moncada S, Vallance P. (1992). Effect of local intra-arterial NG-monomethyl l-arginine in patients with hypertension: the nitric oxide dilator mechanisms appears abnormal. Journal of Hypertension, 10, 1025-1031.
• Cediel E, Vazquez-Cruz B, Navarro-Cid J, de las Heras N, Sanz-Rosa D, Cachofeiro V, Lahera V. (2002). Role of endothelin-1 and thromboxane A2 in renal vasoconstriction induced by angiotensin II in diabetes and hypertension. Kidney International. Supplement 62(82), 2–7.
• Changbin Q, Baylis C. (2000). Dexamethasone worsens nitric oxide inhibition-induced hypertension and renal dysfunction. American Journal of Hypertension, 13(10), 1097–2002.
• Franco-Colin M, Villanueva I, Pinon M, Racotta R. (2006). The effects of sympathectomy and dexamethasone in rats ingesting sucrose. International Journal of Biological Sciences, 2(1), 17-22.
• Francois H, Makhanova N, Ruiz P, Ellison J, Mao L, Rockman HA, Coffman TM. (2008). A role for the thromboxane receptor in l-NAME hypertension. American journal of physiology. Renal Physiology, 295(4), 1096–1102.
• Giani JF, Janjulia T, Kamat N, Seth DM, Blackwell LBW, Shah KH, Shen XZ, Fuchs S, Delpire E, Toblli JE, Bernstein KE, McDonough AA, Gonzalez-Villalobos RA. (2014). Renal angiotensin-converting enzyme is essential for the hypertension induced by nitric oxide synthesis inhibition. Journal of the American Society of Nephrology, 25(12), 2752–2763.
• Goodwin JE, Zhang J, Gonzalez D, Albinsson S, Geller DS. (2011). Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension. Jornal of Hypertension, 29(7), 1347-1356.
• Jennings AS, Ferguson DC. (1984). Effect of dexamethasone on triiodothyronine production in the perfused rat liver and kidney. Endocrinology, 114(1), 31-36.
• Kemse NG, Kale AA, Joshi SR. (2014). A combined supplementation of omega-3 fatty acids and micro nutrients (folic acid, vitamin B12) reduces oxidative stress markers in a rat model of pregnancy induced hypertension. PLoS One, 9(11), 111902.
• Koricanac G, Isenovic E, Stojanovic-Susulic V, Miskovic D, Zakula Z, Ribarac-Stepic N. (2006). Time dependent effects of dexamethasone on serum insulin level and insulin receptors in rat liver and erythrocytes. General Physiology and Biophysics, 25(1), 11-24.
• Kriska T, Cepura C, Gauthier KM, Campbell WB. (2014). Role of macrophage PPARγ in experimental hypertension. American journal of physiology. Heart and Circulatory Physiology, 306(1), 26–32.
• Lesniewska B, Nowak KW, Malendowicz LK. (1992). Dexamethasone-induced adrenal cortex atrophy and recovery of the gland from partial, steroid-induced atrophy. Experimental and Clinical Endocrinology, 100(3), 133-139.
• Li L, Storey P, Kim D, Li W, Prasad P. (2003). Kidneys in hypertensive rats show reduced response to nitric oxide synthase inhibition as evaluated by BOLD MRI. Journal of Magnetic Resonance Imaging, 17(6), 671–675.
• Li M, Dusting GJ,Whitworth JA. (1992). Inhibition of NO synthesis has an additive effect on hypertension induced by ACTH in conscious rats. Clinical and Experimental Pharmacology and Physiology, 19(10), 675-681.
• Liu Y, Mladinov D, Pietrusz JL, Usa K, Liang M. (2009). Glucocorticoid response elements and11β-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression. Cardiovascular Research Journal, 81(1), 140–147.
• Losonczy G, Mucha I, Müller V, Kriston T, Ungvari Z, Tornóci L, Rosivall L, Venuto R. (1996). The vasoconstrictor effects of L-NAME, a nitric oxide synthase inhibitor, in pregnant rabbits. British Journal of Pharmacology, 118(4), 1012–1018.
• Lou YK, Wen C, Li M, Adams DJ, Wang MX, Yang F, Morris BJ, Whitworth JA. (2001). Decreased renal expression of nitricoxide synthase isoforms in adrenocorticotropin-induced and corticosterone-induced hypertension. Hypertension, 37(4), 1164-1170.
• Michel C, Cabanac M. (1999). Effects of dexamethasone on the body weight set point of rats. Physiology and Behavior, 68(1), 145–150.
• Mostello DJ, Hamosh M, Hamosh P. (1981). Effect of dexamethasone on lipoprotein lipase activity of fetal rat lung. Biolology of the Neonate, 40, 121–128.
• Motta K, Ruiz MF, Bordin S and Rafacho A. (2015). Evaluation of lipid homeostasis in the late gestational period of rats exposed to dexamethasone. Diabetology and Metabolic Syndrome, 7(1), 74.
• Nathan L, Cuevas J, Chaudhuri G. (1995). The role of nitric oxide in the altered vascular reactivity of pregnancy in the rat. British Journal of Pharmacology, 114(5), 955–960.
• Osol G, Barron C, Gokina N, Mandala M. (2009). Inhibition of nitric oxide synthases abrogates pregnancy-induced uterine vascular expansive remodeling. Journal of Vascular Research, 46(5), 478-486.
• Pennington KA, Schlitt JM, Jackson DL, Schulz LC, Schust DJ. (2012). Preeclampsia: multiple approaches for a multifactorial disease. Disese Models and Mechanisms, 5(1), 9–18.
• Podjarny E , Losonczy G and Baylis C. (2004). Animal models in preeclampsia. Seminars in Nephrology, 24(6), 596-606.
• Púzserová A, Csizmadiová Z, Bernátová I. (2007). Effect of blood pressure on L-NAME-sensitive component of vasorelaxation in adult rats. Physiological Research, 56 (Suppl. 2), S77-S84.
• Qiu C, Muchant D, Beierwaltes WH, Racusen L, Baylis C. (1998). Evolution of chronic nitricoxide inhibition hypertension: relationship to renal function. Hypertension, 31(1), 21-26.
• Rafikov R, Fonseca FV, Kumar S, Pardo D, Darragh C, Elms S, Fulton D, Black SM. (2011). eNOS activation and NO function: structural motifs responsible for the post translational control of endothelial nitric oxide synthase activity. Journal of Endocrinology, 210(3), 271-284.
• Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM, Zatz R. (1992). Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. Hypertension, 20(3), 298-303.
• Roberts CK, Vaziri ND, Wang XQ, Barnard RJ. (2000). Enhanced NO inactivation and hypertension induced by a high-fat, refined-carbohydrate diet. Hypertension, 36, 423-429.
• Rooman R, Koster G, Bloemen R, Gresnigt R, van Buul-Offers SC. (1999). The effect of dexamethasone on body and or gan growth of normal and IGF-II-transgenic mice. Journal of Endocrinology, 163(3), 543-552.
• Safaeian L, Ghannadi A, Javanmard SH, Vahidian MH. (2015). The effect of hydroalcoholic extract of ferula foetida stems on blood pressure and oxidative stress in dexamethasone-induced hypertensive rats. Research in Pharmaceutical Sciences, 10(4), 326-334.
• Sood A, Ismail-Beigi F. (2010). Effect of dexamethasone on insulin secretion: examination of under lying mechanisms. Endocrine Practice, 16(5), 763-769.
• Tain YL, Chen CC, Sheen JM, Yu HR, Tiao MM, Kuo HC, Huang LT. (2014). Melatonin attenuates prenatal dexamethasone-induced blood pressure increase in a rat model. Journal of the American Society of Hypertension, 8(4), 216-226.
• Tong YC, Wang CJ, Cheng JT. (1997). The role of nitric oxide in the control of plasma glucoseconcentration in spontaneously hypertensive rats. Neuroscience Letters, 233(2-3), 93-96.
• Tonolo G, Fraser R, Connell JM, Kenyon CJ. (1988). Chronic low-dose infusions of dexamethasone in rats: effects on blood pressure, body weight and plasma atrial natriuretic peptide. Jornal of Hypertension, 6(1), 25-31.
• Török J. (2008). Participation of nitric oxide in different models of experimental hypertension. Physiological Research, 57(6), 813–825.
• Troiano JA, Potje SR, Graton ME, Cavalari P, Pereira AA, Vale GT, Nakamune AC, Sumida DH, Tirapelli CR, Antonialli C. (2016). Decreased reactive oxygen species production and NOX1, NOX2, NOX4 expression contribute to hyporeactivity to phenylephrine in aortas of pregnant SHR. Life Sciences Journal, 144, 178-184.
• Wallerath T, Witte K, Schafer SC, Schwarz PM, Prellwitz W, Wohlfart P, Kleinert H, Lehr HA, Lemmer B, Förstermann U. (1999). Down-regulation of the expression of endothelial NO synthase is likely to contribute to glucocorticoid-mediated hypertension. Proceedings of the National Academy of Sciences of the United States of America, 96(23), 13357–13362.
• Wen C, Li M, Whitworth JA. (2000). Role of nitric oxide in adrenocorticotrophin-induced hypertension: L-arginine effects reversed by N-nitro-L-arginine. Clinical and Experimental Pharmacology and Physiology, 27(11), 887-890.
• WHO. (2005). Risking death to give life. World Health Organization, Geneva, Switzerland.Yallampalli C, Byam-Smith M, Nelson S, Garfield RE. (1994). Steroid hormones modulate the production of nitric oxide and cGMP in the rat uterus. Endocrinology, 134, 1971-1974.
• Zhang LN, Ji LD, Fei LJ, Yuan F, Zhang YM, Xu J. (2013). Association between polymorphisms of alpha-adducin gene and essential hypertension in Chinese population. BioMed Research International, 2013:451094. doi: 10.1155/2013/451094.