NOS Inhibition-Induced Hypertension: Comparision of Stable and Gradual Dose of L-NNA Administration in Rats

Yıl 2007, Cilt: 12 Sayı: 4, 251 - 255, 01.08.2007

Süleyman Oktar Engin Yılmaz Engin Şahna Hakkı Engin Aksulu

Öz

Objective: Chronic NOS inhibition-induced hypertension model is used commonly in essential hypertension researches. All these studies investigated using a stable doses of NOS inhibitor agents over experimental progress. But, it is decreased gradually synthesis and/or release of NO in essential hypertension. To better mimic essential hypertension, the doses of L-NNA (a NOS inhibitor) was administrated gradually increasing and was compared group of stable dose. Material and Method: Wistar rats were divided into 3 groups. Control group was done any administration. Second group took the stable concentration of L-NNA over 3 weeks and third group took gradually increasing concentration of L-NNA for 3 weeks. Blood pressure and heart rate are measured by tail-cuff method. Plasma nitrite/nitrate levels and kidney/body weigth ratios were also compared. Results: In the stable dose administrated group, heart rates decreased while the blood pressure increased. On the other hand, in the gradually increasing doses of L-NNA administrated group, heart rates did not change despite the increasing blood pressure. Plasma nitrite/nitrate levels decreased significantly but there was any change in kidney/body weight indexes in groups. Conclusion: It is suggested that is associated more gradually NOS inhibition than stable NOS inhibition with essential hypertension. ©2007, Fırat Uiversity, Medical Faculty

Anahtar Kelimeler

-

NOS İnhibisyonu Aracılı Hipertansiyon: Sıçanlarda Sabit ve Kademeli doz L-NNA Uygulamalarının Karşılaştırılması

Öz

Amaç: Esansiyel hipertansiyon araştırmalarında yoğun olarak kullanılan kronik NOS inhibisyonu aracılı hipertansiyonda, bugüne kadar NOS inhibitörü ajanlar deney boyunca sabit dozlarda kullanılmıştır. Oysa esansiyel hipertansiyonda NO sentez ve/veya salıverilmesi progresif olarak azalmaktadır. Esansiyel hipertansiyonu daha iyi taklit etmek için bir NOS inhibitörü olan L-NNA giderek artan dozlarda uygulandı ve kan basıncı gelişimine etkileri sabit doz L-NNA uygulamasıyla karşılaştırıldı. Gereç ve Yöntem: Wistar sıçanlar 3 gruba ayrıldı: Kontrol grubuna deney süresince hiçbir uygulama yapılmadı. İkinci gruba L-NNA dozu sabit ve üçüncü gruba ise her hafta kademeli bir şekilde arttırılarak 3 hafta boyunca uygulandı. Kan basıncı ve kalp hızları tail-cuff metodu ile ölçüldü. Ayrıca, plazma nitrit/nitrat seviyeleri ve böbrek/vücut ağırlığı indeksleri karşılaştırıldı. Bulgular: Sabit doz L-NNA alan grubun kan basıncı artarken kalp hızının düştüğü, fakat L-NNA dozu kademeli olarak uygulandığında kan basıncı yükselmesine rağmen kalp hızında bir düşme olmadığı tespit edildi. Her iki grubun plazma nitrit/nitrat seviyeleri anlamlı düşerken böbrek/vücut ağırlığı indekslerinde bir değişiklik tespit edilmedi. Sonuç: NOS inhibisyonunun kademeli olarak artırılmasıyla kan basıncı artmasına rağmen kalp hızının değişmemesi, bu modelin sabit doz NOS inhibisyonuna göre esansiyel hipertansiyonla daha ilişki olabileceğine işaret etmektedir. ©2007, Fırat Üniversitesi, Tıp Fakültesi

Anahtar Kelimeler

Nitrik Oksit/Eksiklik, Hipertansiyon, Kalp Hızı

Kaynakça

• Yilmaz G, Aksulu HE, Demirel E, et al. Modulation by endothelium of the vascular effects of angiotensin II. Agents Actions 1987; 21: 184-190.
• Hill C, Lateef AM, Engels K, Samsell L, Baylis C. Basal and stimulated nitric oxide in control of kidney function in the aging rat. Am J Physiol 1997; 272: 1747-1753.
• Aksulu HE, Cellek S, Turker RK. Cholesterol feeding attenuates endothelium-dependent relaxation response to acetylcholine in the main pulmonary artery of chickens. Eur J Pharmacol 1986; 129: 397-400.
• Linder L, Kiowski W, Buhler FR, Luscher TF. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation 1990; 81: 1762-1767.
• Moncada S, Palmer RM, Higgs EA. Nitric oxide. physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43: 109-142.
• Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM, Zatz R. Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. Hypertension 1992; 20: 298-303.
• Tugrul I, Oktar S, Deniz E, Yılmaz, E, Aksulu HE. NOS inhibition mediated hypertension: High and low doses of L-NNA administration. In Turkish Pharmacological Society, 17th National Congress of Pharmacology, Antalya/TURKEY, 2003.
• Zatz R, Baylis C. Chronic nitric oxide inhibition model six years on. Hypertension 1998; 32: 958-964.
• Yuasa S, Li X, Hitomi H, et al. Sodium sensitivity and sympathetic nervous system in hypertension induced by longterm nitric oxide blockade in rats. Clin Exp Pharmacol Physiol 2000; 27: 18-24.
• Vapaatalo H, Mervaala E, Nurminen ML. Role of endothelium and nitric oxide in experimental hypertension. Physiol Res 2000; 49: 1-10.
• Taddei S, Virdis A, Ghiadoni L, et al. Age-related reduction of NO availability and oxidative stress in humans. Hypertension 2001; 38: 274-279.
• Zavaroni I, Ardigo D, Rossi PC, et al. Relationship between plasma nitric oxide concentration and insulin resistance in essential hypertension. Am J Hypertens 2004; 17: 549-552.
• Yılmaz E. Sıçanlarda Plazma Nitrik Oksit Düzeylerinin Ölçümü: Elektrokimyasal ve Spektrofotometrik Yöntemlerin Karşılaştırılması. Yüksek Lisans Tezi, Elazığ: Fırat Üniversitesi Tıp Fakültesi, Farmakoloji Anabilim Dalı, 2004.
• Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990; 36: 1440-1443.
• Armas-Padilla MC, Armas-Hernandez MJ, Sosa-Canache B, et al. Nitric oxide and malondialdehyde in human hypertension. Am J Ther 2007; 14: 172-176.
• Kedziora-Kornatowska K, Kornatowski T, Bartosz G, et al. Production of nitric oxide, lipid peroxidation and oxidase activity of ceruloplasmin in blood of elderly patients with primary hypertension. Effects of perindopril treatment. Aging Clin Exp Res 2006; 18: 1-6.
• Di Massimo C, Scarpelli P, Di Lorenzo N, et al. Impaired plasma nitric oxide availability and extracellular superoxide dismutase activity in healthy humans with advancing age. Life Sci 2006; 78: 1163-1167.
• Izzo JL, Black HR. Primer Hipertansiyon. Kazancı G (Çeviren). 3.Baskı, Đstanbul: Nobel, 2004.
• Scrogin KE, Hatton DC, Chi Y, Luft FC. Chronic nitric oxide inhibition with L-NAME: effects on autonomic control of the cardiovascular system. Am J Physiol 1998; 274: 367-374.
• Okazaki H, Minamino T, Tsukamoto O, et al. Angiotensin II type 1 receptor blocker prevents atrial structural remodeling in rats with hypertension induced by chronic nitric oxide inhibition. Hypertens Res 2006; 29: 277-284.
• Hu L, Manning RD, Jr., Brands MW. Long-term cardiovascular role of nitric oxide in conscious rats. Hypertension 1994; 23: 185194.
• Loichot C, Cazaubon C, Grima M, et al. Vasopressin does not effect hypertension caused by long-term nitric oxide inhibition. Hypertension 2000; 35: 602-608.
• Dananberg J, Sider RS, Grekin RJ. Sustained hypertension induced by orally administered nitro-L-arginine. Hypertension 1993; 21: 359-363.
• Matsuoka H, Nishida H, Nomura G, Van Vliet BN, Toshima H. Hypertension induced by nitric oxide synthesis inhibition is renal nerve dependent. Hypertension 1994; 23: 971-975.
• Ferrieres J, Ruidavets JB. Association between resting heart rate and hypertension treatment in a general population. Am J Hypertens 1999; 12: 628-631.
• Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Mancia G. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension 1998; 31: 68-72.