Nehir Sucu Nehir Sucu TIP FAKÜLTESİ CERRAHİ TIP BİLİMLERİ BÖLÜMÜ KALP VE DAMAR CERRAHİSİ ANABİLİM DALI
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Pharmacological Inhibition of Mammalian Target of Rapamycin Attenuates Deoxycorticosterone Acetate Salt–Induced Hypertension and Related Pathophysiology: Regulation of Oxidative Stress, Inflammation, and Cardiovascular Hypertrophy in Male Rats

Temiz Reşitoğlu, Meryem | Sucu, Nehir | Kibar, Deniz | Yılmaz, Şakir Necat | Tunçtan, Bahar | Şahan Fırat, Seyhan

The present study aimed to explore the contribution of mammalian target of rapamycin (mTOR) in deoxycorticosterone acetate (DOCA) salt–induced hypertension and related pathophysiological changes in cardiovascular and renal tissues. DOCA salt loading resulted in an increase in systolic blood pressure, diastolic blood pressure, and mean blood pressure along with the activity of ribosomal protein S6, the effector protein of mTOR. Treatment with rapamycin, the selective inhibitor of mTOR, initiated at the fourth week of DOCA- salt administration normalized the systolic blood pressure and attenuated ribosomal protein S6 activity in the heart, aorta, and kidney. Cardiac and vascular hypertrophy, oxidative stress, and infiltration of macrophages (CD68+), the marker of inflammation, were also reduced in rapamycin-treated, DOCA-salt, hypertensive rats. In addition, renal hypertrophy and dysfunction were also reduced with rapamycin-treated hypertensive rats. Moreover, these pathophysiological changes in DOCA-salt hypertensive rats were associated with increased NADPH oxidase (NOX) activity, gp91phox (formerly NOX2) expression, ERK1/2, and p38 MAPK activities in the heart, aorta, and kidney were minimized by rapamycin. These data indicate that mTOR plays an important role in regulating bloo...

N -Acetylcysteine-induced vasodilatation is modulated by K ATP channels, Na /K -ATPase activity and intracellular calcium concentration: An in vitro study

Çömelekoğlu, Ülkü | Sucu, Nehir | Yalın, Ali Erdinç | Yılmaz, Şakir Necat | Yalın, Serap | Söğüt, Fatma | Kibar, Kezban | Akkapulu, Merih

Background In this study, we aimed to investigate the role of ATP-sensitive potassium (KATP) channel, Na+/K+-ATPase activity, and intracellular calcium levels on the vasodilatory effect of N-acetylcysteine (NAC) in thoracic aorta by using electrophysiological and molecular techniques. Methods Rat thoracic aorta ring preparations and cultured thoracic aorta cells were divided into four groups as control, 2 mM NAC, 5 mM NAC, and 10 mM NAC. Thoracic aorta rings were isolated from rats for measurements of relaxation responses and Na+/K+-ATPase activity. In the cultured thoracic aorta cells, we measured the currents of KATP channel, the concentration of intracellular calcium and mRNA expression level of KATP channel subunits (KCNJ8, KCNJ11, ABCC8 and ABCC9). Results The relaxation rate significantly increased in all NAC groups compared to control. Similarly, Na+/K+- ATPase activity also significantly decreased in NAC groups. Outward KATP channel current significantly increased in all NAC groups compared to the control group. Intracellular calcium concentration decreased significantly in all groups with compared control. mRNA expression level of ABCC8 subunit significantly increased in all NAC groups compared to the control group. Pearson correlation analysis showed that relaxatio...