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Effect of swimming exercise on angiotensin-(1–7)-mediated aortic dilation responses in the nitric oxide synthase inhibition-induced hypertensive rats

Year 2025, Volume: 50 Issue: 4, 1092 - 1102, 22.12.2025
https://doi.org/10.17826/cumj.1753982

Abstract

Purpose: Regular exercise exerts at least some of its effects on lowering high blood pressure by regulating vascular tone. Angiotensin-(1-7) [Ang-(1-7)], a member of the renin–angiotensin system (RAS), has antihypertensive and vasodilator effects. The aim of this study is to investigate whether the blood pressure-lowering effect of regular exercise is mediated by Ang-(1-7)-induced vasodilation in a nitric oxide synthase (NOS) inhibition-induced hypertension model.
Materials and Methods: 8-week-old Wistar male rats were separated into four groups: Control (C), Hypertension (H), Exercise (E), and Hypertension+Exercise (HE). Rats were subjected to the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME,25 mg.kg-1.day-1) in drinking water and swimming (1 hour/day, 5 days/week) to create hypertension and/or exercise models. Ang-(1-7)-induced dilation responses of aortas were examined in the presence/absence of NOS, cyclooxygenase (COX), and endothelium-derived hyperpolarizing factor (EDHF) inhibitors. To assess the roles of the Mas receptor (MasR) and the Angiotensin II-Type2 receptor (AT2R) in Ang-(1-7)-induced vasodilation, the MasR antagonists A-779 and D-Pro⁷-Ang-(1-7), and AT2R inhibitor PD123319 were used.
Results: Swimming exercise improved Ang-(1-7)-mediated vasodilation responses in the E but not in the HE group. Inhibition of NOS and EDHF pathways diminished Ang-(1-7)-induced vasodilation responses in all groups. While vasodilator responses were attenuated only by D-Pro⁷-Ang-(1-7) in the C group, both MasR antagonists reduced these responses in the E and HE groups. In the H group, Ang-(1-7)-induced vasodilation was decreased in the presence of both D-Pro⁷-Ang-(1-7) and PD123319.
Conclusion: Although swimming exercise did not significantly alter Ang-(1-7)-mediated vasodilatory responses in the NOS-inhibited hypertensive model, an enhanced involvement of MasR receptors was observed in the vasodilation responses of the exercise groups, particularly through NOS and EDHF pathways.

Project Number

Akdeniz University Scientific Research Projects Coordination Unit: TDK-2018-4057

References

  • Ma J, Chen X. Advances in pathogenesis and treatment of essential hypertension. Front Cardiovasc Med. 2022;9:1003852.
  • Martyniak A, Tomasik PJ. A New Perspective on the Renin-Angiotensin System. Diagnostics (Basel). 2022;13:16.
  • Yang R, Smolders I, Dupont AG. Blood pressure and renal hemodynamic effects of angiotensin fragments. Hypertens Res. 2011;34:674-83.
  • Silva GM, Franca-Falcao MS, Calzerra NTM, Luz MS, Gadelha DDA, Balarini CM et al. Role of Renin-Angiotensin System Components in Atherosclerosis: Focus on Ang-II, ACE2, and Ang-1-7. Front Physiol. 2020;11:1067.
  • Zhang F, Tang H, Sun S, Luo Y, Ren X, Chen A et al. Angiotensin-(1-7) induced vascular relaxation in spontaneously hypertensive rats. Nitric Oxide. 2019;88:1-9.
  • Zhang F, Xu Y, Pan Y, Sun S, Chen A, Li P et al. Effects of Angiotensin-(1-7) and Angiotensin II on Acetylcholine-Induced Vascular Relaxation in Spontaneously Hypertensive Rats. Oxid Med Cell Longev. 2019;2019:6512485.
  • Yousif MHM, Benter IF, Diz DI, Chappell MC. Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity. Peptides. 2017;90:10-16.
  • de Moraes PL, Kangussu LM, Castro CH, Almeida AP, Santos RAS, Ferreira AJ. Vasodilator Effect of Angiotensin-(1-7) on Vascular Coronary Bed of Rats: Role of Mas, ACE and ACE2. Protein Pept Lett. 2017;24:869-75.
  • Silva DM, Gomes-Filho A, Olivon VC, Santos TM, Becker LK, Santos RA et al. Swimming training improves the vasodilator effect of angiotensin-(1-7) in the aorta of spontaneously hypertensive rat. J Appl Physiol (1985). 2011;111:1272-7.
  • Endlich PW, Claudio ER, Lima LC, Ribeiro Junior RF, Peluso AA, Stefanon I et al. Exercise modulates the aortic renin-angiotensin system independently of estrogen therapy in ovariectomized hypertensive rats. Peptides. 2017;87:41-49.
  • Gu Q, Wang B, Zhang XF, Ma YP, Liu JD, Wang XZ. Contribution of renin-angiotensin system to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats. Cardiovasc Pathol. 2014;23:298-305.
  • Clark CR, Khalil RA. Regulation of vascular angiotensin II type 1 and type 2 receptor and angiotensin-(1-7)/MasR signaling in normal and hypertensive pregnancy. Biochem Pharmacol. 2024;220:115963.
  • Drozdz D, Drozdz M, Wojcik M. Endothelial dysfunction as a factor leading to arterial hypertension. Pediatr Nephrol. 2023;38:2973-85.
  • Ambrosino P, Bachetti T, D'Anna SE, Galloway B, Bianco A, D'Agnano V et al. Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension. J Cardiovasc Dev Dis. 2022;9:136.
  • Ahmad A, Dempsey SK, Daneva Z, Azam M, Li N, Li PL et al. Role of nitric oxide in the cardiovascular and renal systems. Int J Mol Sci. 2018;19:2605.
  • Hermann M, Flammer A, Luscher TF. Nitric oxide in hypertension. J Clin Hypertens (Greenwich). 2006;8:17-29.
  • Campbell DJ. L-NAME hypertension: trying to fit the pieces together. J Hypertens. 2006;24:33-6.
  • Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension. 2005;46:667-75.
  • Kuru O, Senturk UK, Kocer G, Ozdem S, Baskurt OK, Cetin A et al. Effect of exercise training on resistance arteries in rats with chronic NOS inhibition. J Appl Physiol (1985). 2009;107:896-902.
  • Magalhaes DM, Nunes-Silva A, Rocha GC, Vaz LN, de Faria MHS, Vieira ELM et al. Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system. Heliyon. 2020;6:e03208.
  • Rush JW, Aultman CD. Vascular biology of angiotensin and the impact of physical activity. Appl Physiol Nutr Metab. 2008;33:162-72.
  • Kluskens LD, Nelemans SA, Rink R, de Vries L, Meter-Arkema A, Wang Y et al. Angiotensin-(1-7) with thioether bridge: an angiotensin-converting enzyme-resistant, potent angiotensin-(1-7) analog. J Pharmacol Exp Ther. 2009;328:849-54.
  • Silva DM, Vianna HR, Cortes SF, Campagnole-Santos MJ, Santos RA, Lemos VS. Evidence for a new angiotensin-(1-7) receptor subtype in the aorta of Sprague-Dawley rats. Peptides. 2007;28:702-7.
  • Lemos VS, Silva DM, Walther T, Alenina N, Bader M, Santos RA. The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of mas-knockout mice. J Cardiovasc Pharmacol. 2005;46:274-9.
  • Gunarathne LS, Rajapaksha IG, Casey S, Qaradakhi T, Zulli A, Rajapaksha H et al. Mas-related G protein-coupled receptor type D antagonism improves portal hypertension in cirrhotic rats. Hepatol Commun. 2022;6:2523-37.
  • Kung CF, Moreau P, Takase H, Luscher TF. L-NAME hypertension alters endothelial and smooth muscle function in rat aorta. Prevention by trandolapril and verapamil. Hypertension. 1995;26:744-51.
  • Hropot M, Grotsch H, Klaus E, Langer KH, Linz W, Wiemer G et al. Ramipril prevents the detrimental sequels of chronic NO synthase inhibition in rats: hypertension, cardiac hypertrophy and renal insufficiency. Naunyn Schmiedebergs Arch Pharmacol. 1994;350:646-52.
  • Srere PA. Controls of citrate synthase activity. Life Sci. 1974;15:1695-710.
  • Manshor NM, Dewa A, Asmawi MZ, Ismail Z, Razali N, Hassan Z. Vascular Reactivity Concerning Orthosiphon stamineus Benth-Mediated Antihypertensive in Aortic Rings of Spontaneously Hypertensive Rats. Int J Vasc Med. 2013;2013:456852.
  • Panza JA. Endothelial dysfunction in essential hypertension. Clin Cardiol. 1997;20:II-26-33.
  • Ozen N, Nasircilar Ulker S, Ulker P, Ozcan F, Aslan M, Senturk UK et al. Effect of 20-HETE inhibition on L-NAME-induced hypertension in rats. Clin Exp Hypertens. 2018;40:292-302.
  • Lou M, Zong XF, Wang LL. Curative treatment of hypertension by physical exercise. Eur Rev Med Pharmacol Sci. 2017;21:3320-26.
  • Koc Yildirim E, Dedeoglu Z, Kaya M, Uner AG. The effect of swimming training on adrenomedullin levels, oxidative stress variables, and gastrocnemius muscle contractile properties in hypertensive rats. Clin Exp Hypertens. 2021;43:131-37.
  • Yim HE, Yoo KH. Renin-Angiotensin system - considerations for hypertension and kidney. Electrolyte Blood Press. 2008;6:42-50.
  • Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100:8258-63.
  • Benter IF, Yousif MH, Anim JT, Cojocel C, Diz DI. Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. Am J Physiol Heart Circ Physiol. 2006;290:H684-91.
  • Olivon VC, Aires RD, Santiago LB, Ramalho LZ, Cortes SF, Lemos VS. Mas receptor overexpression increased Ang-(1-7) relaxation response in renovascular hypertensive rat carotid. Peptides. 2015;71:250-8.
  • Evangelista FS. Physical Exercise and the Renin Angiotensin System: Prospects in the COVID-19. Front Physiol. 2020;11:561403.
  • Brosnihan KB, Li P, Ferrario CM. Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension. 1996;27:523-8.
  • Liu XX, Chen AD, Pan Y, Zhang F, Qi ZB, Cao N et al. [Angiotensin-(1-7) improves endothelium-dependent vasodilation in rats with monocrotaline-induced pulmonary arterial hypertension]. Sheng Li Xue Bao. 2023;75:497-502.
  • Bertagnolli M, Casali KR, De Sousa FB, Rigatto K, Becker L, Santos SH et al. An orally active angiotensin-(1-7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats. Peptides. 2014;51:65-73.
  • Jiang F, Yang J, Zhang Y, Dong M, Wang S, Zhang Q et al. Angiotensin-converting enzyme 2 and angiotensin 1-7: novel therapeutic targets. Nat Rev Cardiol. 2014;11:413-26.
  • Steckelings UM, Widdop RE, Sturrock ED, Lubbe L, Hussain T, Kaschina E et al. The angiotensin AT(2) receptor: from a binding site to a novel therapeutic target. Pharmacol Rev. 2022;74:1051-135.
  • Karnik SS, Singh KD, Tirupula K, Unal H. Significance of angiotensin 1-7 coupling with MAS1 receptor and other GPCRs to the renin-angiotensin system: IUPHAR Review 22. Br J Pharmacol. 2017;174:737-53.
  • Filho AG, Ferreira AJ, Santos SH, Neves SR, Silva Camargos ER, Becker LK et al. Selective increase of angiotensin(1-7) and its receptor in hearts of spontaneously hypertensive rats subjected to physical training. Exp Physiol. 2008;93:589-98.
  • Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003;12:70-88.
  • Ognibene DT, Oliveira PR, Marins de Carvalho LC, Costa CA, Espinoza LA, Criddle DN et al. Angiotensin II-mediated vasodilation is reduced in adult spontaneously hypertensive rats despite enhanced expression of AT2 receptors. Clin Exp Pharmacol Physiol. 2009;36:12-9.
  • Romero-Nava R, Rodriguez JE, Resendiz-Albor AA, Sanchez-Munoz F, Ruiz-Hernandez A, Huang F et al. Changes in protein and gene expression of angiotensin II receptors (AT1 and AT2) in aorta of diabetic and hypertensive rats. Clin Exp Hypertens. 2016;38:56-62.

Nitrik oksit sentaz inhibisyonu ile oluşturulan hipertansiyon modelinde yüzme egzersizinin anjiyotensin-(1–7) aracılı aortik gevşeme yanıtlarına etkisi

Year 2025, Volume: 50 Issue: 4, 1092 - 1102, 22.12.2025
https://doi.org/10.17826/cumj.1753982

Abstract

Amaç: Düzenli egzersizin, yüksek kan basıncını düşürücü etkilerinden biri de vasküler tonusu düzenlemesidir. Renin-anjiyotensin sistemi (RAS)’nin üyesi olan Angiotensin-(1-7) [Ang-(1-7)], antihipertansif ve vazodilatör etkilere sahiptir. Bu çalışmayla nitrik oksit sentaz (NOS) inhibisyonuyla oluşturulan hipertansiyon modelinde; düzenli egzersizin kan basıncını düşürücü etkisinde, Ang (1-7) aracılı gevşeme yanıtlarının aracılık edip etmediği araştırılmıştır.
Gereç ve Yöntem: 8 haftalık erkek Wistar sıçanlar kullanıldı. Sıçanlar; Kontrol (K), Hipertansiyon (H), Egzersiz (E) ve Hipertansiyon+Egzersiz (HE) olmak üzere 4 gruba ayrıldı. Hipertansiyon ve/veya egzersiz modeli oluşturmak için sıçanlara; içme suyunda NOS inhibitorü, Nω-nitro-L-arginine methyl ester (L-NAME,25 mg.kg-1.gün-1) ve egzersiz gruplarına 6 hafta boyunca yüzme egzersizi (1 saat/gün,5 gün/hafta) uygulandı. Deneylerin sonunda NOS, siklooksijenaz (COX) ve endotel kaynaklı hiperpolarize edici faktör (EDHF) inhibitörlerinin varlığında/yokluğunda; sıçan aortlarının Ang-(1-7)-aracılı gevşeme yanıtları incelendi. Ang-(1-7)-aracılı gevşeme yanıtlarına Mas reseptör (MasR) ve Anjiyotensin II-Tip 2 (AT2R) reseptörlerinin katkılarını değerlendirmek amacıyla; MasR antagonistleri olarak A-779 ve D-Pro⁷-Ang-(1-7), AT2 reseptör antagonisti olarak PD123,319 kullanıldı.
Bulgular: Yüzme egzersizi; E grubunda Ang-(1-7)-aracılı damar gevşeme yanıtlarında artışa neden olurken, HE grubunda böyle bir etki izlenmedi. NOS ve EDHF yolaklarının inhibisyonu tüm grupların Ang-(1-7)-aracılı gevşeme yanıtlarında azalmaya sebep oldu. K grubunda gevşeme yanıtı yalnızca D-Pro⁷-Ang-(1-7) uygulaması ile azalırken; E ve HE gruplarında gevşeme yanıtlarındaki azalma her iki MasR antagonistinin uygulanmasıyla da gözlendi. H grubundaki Ang-(1-7)-aracılı gevşeme yanıtı, D-Pro⁷-Ang-(1-7) ve PD123,319 antagonistleri varlığında azaldı.
Sonuç: Yüzme egzersizi, NOS-inhibisyonuyla indüklenen hipertansiyon modelinde Ang-(1-7)-aracılı gevşeme yanıtları üzerine istatistiksel olarak anlamlı bir etki oluşturmadı. Ancak egzersiz gruplarından elde edilen gevşeme yanıtlarında MasR’lerinin katkısının daha fazla olduğu ayrıca NOS ve EDHF yolaklarının MasR aracılı gevşeme yanıtlarına aracılık ettiği saptandı.

Project Number

Akdeniz University Scientific Research Projects Coordination Unit: TDK-2018-4057

References

  • Ma J, Chen X. Advances in pathogenesis and treatment of essential hypertension. Front Cardiovasc Med. 2022;9:1003852.
  • Martyniak A, Tomasik PJ. A New Perspective on the Renin-Angiotensin System. Diagnostics (Basel). 2022;13:16.
  • Yang R, Smolders I, Dupont AG. Blood pressure and renal hemodynamic effects of angiotensin fragments. Hypertens Res. 2011;34:674-83.
  • Silva GM, Franca-Falcao MS, Calzerra NTM, Luz MS, Gadelha DDA, Balarini CM et al. Role of Renin-Angiotensin System Components in Atherosclerosis: Focus on Ang-II, ACE2, and Ang-1-7. Front Physiol. 2020;11:1067.
  • Zhang F, Tang H, Sun S, Luo Y, Ren X, Chen A et al. Angiotensin-(1-7) induced vascular relaxation in spontaneously hypertensive rats. Nitric Oxide. 2019;88:1-9.
  • Zhang F, Xu Y, Pan Y, Sun S, Chen A, Li P et al. Effects of Angiotensin-(1-7) and Angiotensin II on Acetylcholine-Induced Vascular Relaxation in Spontaneously Hypertensive Rats. Oxid Med Cell Longev. 2019;2019:6512485.
  • Yousif MHM, Benter IF, Diz DI, Chappell MC. Angiotensin-(1-7)-dependent vasorelaxation of the renal artery exhibits unique angiotensin and bradykinin receptor selectivity. Peptides. 2017;90:10-16.
  • de Moraes PL, Kangussu LM, Castro CH, Almeida AP, Santos RAS, Ferreira AJ. Vasodilator Effect of Angiotensin-(1-7) on Vascular Coronary Bed of Rats: Role of Mas, ACE and ACE2. Protein Pept Lett. 2017;24:869-75.
  • Silva DM, Gomes-Filho A, Olivon VC, Santos TM, Becker LK, Santos RA et al. Swimming training improves the vasodilator effect of angiotensin-(1-7) in the aorta of spontaneously hypertensive rat. J Appl Physiol (1985). 2011;111:1272-7.
  • Endlich PW, Claudio ER, Lima LC, Ribeiro Junior RF, Peluso AA, Stefanon I et al. Exercise modulates the aortic renin-angiotensin system independently of estrogen therapy in ovariectomized hypertensive rats. Peptides. 2017;87:41-49.
  • Gu Q, Wang B, Zhang XF, Ma YP, Liu JD, Wang XZ. Contribution of renin-angiotensin system to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats. Cardiovasc Pathol. 2014;23:298-305.
  • Clark CR, Khalil RA. Regulation of vascular angiotensin II type 1 and type 2 receptor and angiotensin-(1-7)/MasR signaling in normal and hypertensive pregnancy. Biochem Pharmacol. 2024;220:115963.
  • Drozdz D, Drozdz M, Wojcik M. Endothelial dysfunction as a factor leading to arterial hypertension. Pediatr Nephrol. 2023;38:2973-85.
  • Ambrosino P, Bachetti T, D'Anna SE, Galloway B, Bianco A, D'Agnano V et al. Mechanisms and Clinical Implications of Endothelial Dysfunction in Arterial Hypertension. J Cardiovasc Dev Dis. 2022;9:136.
  • Ahmad A, Dempsey SK, Daneva Z, Azam M, Li N, Li PL et al. Role of nitric oxide in the cardiovascular and renal systems. Int J Mol Sci. 2018;19:2605.
  • Hermann M, Flammer A, Luscher TF. Nitric oxide in hypertension. J Clin Hypertens (Greenwich). 2006;8:17-29.
  • Campbell DJ. L-NAME hypertension: trying to fit the pieces together. J Hypertens. 2006;24:33-6.
  • Cornelissen VA, Fagard RH. Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension. 2005;46:667-75.
  • Kuru O, Senturk UK, Kocer G, Ozdem S, Baskurt OK, Cetin A et al. Effect of exercise training on resistance arteries in rats with chronic NOS inhibition. J Appl Physiol (1985). 2009;107:896-902.
  • Magalhaes DM, Nunes-Silva A, Rocha GC, Vaz LN, de Faria MHS, Vieira ELM et al. Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system. Heliyon. 2020;6:e03208.
  • Rush JW, Aultman CD. Vascular biology of angiotensin and the impact of physical activity. Appl Physiol Nutr Metab. 2008;33:162-72.
  • Kluskens LD, Nelemans SA, Rink R, de Vries L, Meter-Arkema A, Wang Y et al. Angiotensin-(1-7) with thioether bridge: an angiotensin-converting enzyme-resistant, potent angiotensin-(1-7) analog. J Pharmacol Exp Ther. 2009;328:849-54.
  • Silva DM, Vianna HR, Cortes SF, Campagnole-Santos MJ, Santos RA, Lemos VS. Evidence for a new angiotensin-(1-7) receptor subtype in the aorta of Sprague-Dawley rats. Peptides. 2007;28:702-7.
  • Lemos VS, Silva DM, Walther T, Alenina N, Bader M, Santos RA. The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of mas-knockout mice. J Cardiovasc Pharmacol. 2005;46:274-9.
  • Gunarathne LS, Rajapaksha IG, Casey S, Qaradakhi T, Zulli A, Rajapaksha H et al. Mas-related G protein-coupled receptor type D antagonism improves portal hypertension in cirrhotic rats. Hepatol Commun. 2022;6:2523-37.
  • Kung CF, Moreau P, Takase H, Luscher TF. L-NAME hypertension alters endothelial and smooth muscle function in rat aorta. Prevention by trandolapril and verapamil. Hypertension. 1995;26:744-51.
  • Hropot M, Grotsch H, Klaus E, Langer KH, Linz W, Wiemer G et al. Ramipril prevents the detrimental sequels of chronic NO synthase inhibition in rats: hypertension, cardiac hypertrophy and renal insufficiency. Naunyn Schmiedebergs Arch Pharmacol. 1994;350:646-52.
  • Srere PA. Controls of citrate synthase activity. Life Sci. 1974;15:1695-710.
  • Manshor NM, Dewa A, Asmawi MZ, Ismail Z, Razali N, Hassan Z. Vascular Reactivity Concerning Orthosiphon stamineus Benth-Mediated Antihypertensive in Aortic Rings of Spontaneously Hypertensive Rats. Int J Vasc Med. 2013;2013:456852.
  • Panza JA. Endothelial dysfunction in essential hypertension. Clin Cardiol. 1997;20:II-26-33.
  • Ozen N, Nasircilar Ulker S, Ulker P, Ozcan F, Aslan M, Senturk UK et al. Effect of 20-HETE inhibition on L-NAME-induced hypertension in rats. Clin Exp Hypertens. 2018;40:292-302.
  • Lou M, Zong XF, Wang LL. Curative treatment of hypertension by physical exercise. Eur Rev Med Pharmacol Sci. 2017;21:3320-26.
  • Koc Yildirim E, Dedeoglu Z, Kaya M, Uner AG. The effect of swimming training on adrenomedullin levels, oxidative stress variables, and gastrocnemius muscle contractile properties in hypertensive rats. Clin Exp Hypertens. 2021;43:131-37.
  • Yim HE, Yoo KH. Renin-Angiotensin system - considerations for hypertension and kidney. Electrolyte Blood Press. 2008;6:42-50.
  • Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100:8258-63.
  • Benter IF, Yousif MH, Anim JT, Cojocel C, Diz DI. Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. Am J Physiol Heart Circ Physiol. 2006;290:H684-91.
  • Olivon VC, Aires RD, Santiago LB, Ramalho LZ, Cortes SF, Lemos VS. Mas receptor overexpression increased Ang-(1-7) relaxation response in renovascular hypertensive rat carotid. Peptides. 2015;71:250-8.
  • Evangelista FS. Physical Exercise and the Renin Angiotensin System: Prospects in the COVID-19. Front Physiol. 2020;11:561403.
  • Brosnihan KB, Li P, Ferrario CM. Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension. 1996;27:523-8.
  • Liu XX, Chen AD, Pan Y, Zhang F, Qi ZB, Cao N et al. [Angiotensin-(1-7) improves endothelium-dependent vasodilation in rats with monocrotaline-induced pulmonary arterial hypertension]. Sheng Li Xue Bao. 2023;75:497-502.
  • Bertagnolli M, Casali KR, De Sousa FB, Rigatto K, Becker L, Santos SH et al. An orally active angiotensin-(1-7) inclusion compound and exercise training produce similar cardiovascular effects in spontaneously hypertensive rats. Peptides. 2014;51:65-73.
  • Jiang F, Yang J, Zhang Y, Dong M, Wang S, Zhang Q et al. Angiotensin-converting enzyme 2 and angiotensin 1-7: novel therapeutic targets. Nat Rev Cardiol. 2014;11:413-26.
  • Steckelings UM, Widdop RE, Sturrock ED, Lubbe L, Hussain T, Kaschina E et al. The angiotensin AT(2) receptor: from a binding site to a novel therapeutic target. Pharmacol Rev. 2022;74:1051-135.
  • Karnik SS, Singh KD, Tirupula K, Unal H. Significance of angiotensin 1-7 coupling with MAS1 receptor and other GPCRs to the renin-angiotensin system: IUPHAR Review 22. Br J Pharmacol. 2017;174:737-53.
  • Filho AG, Ferreira AJ, Santos SH, Neves SR, Silva Camargos ER, Becker LK et al. Selective increase of angiotensin(1-7) and its receptor in hearts of spontaneously hypertensive rats subjected to physical training. Exp Physiol. 2008;93:589-98.
  • Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003;12:70-88.
  • Ognibene DT, Oliveira PR, Marins de Carvalho LC, Costa CA, Espinoza LA, Criddle DN et al. Angiotensin II-mediated vasodilation is reduced in adult spontaneously hypertensive rats despite enhanced expression of AT2 receptors. Clin Exp Pharmacol Physiol. 2009;36:12-9.
  • Romero-Nava R, Rodriguez JE, Resendiz-Albor AA, Sanchez-Munoz F, Ruiz-Hernandez A, Huang F et al. Changes in protein and gene expression of angiotensin II receptors (AT1 and AT2) in aorta of diabetic and hypertensive rats. Clin Exp Hypertens. 2016;38:56-62.
There are 48 citations in total.

Details

Primary Language English
Subjects Sports Medicine, Medical Biochemistry - Proteins, Peptides and Proteomics
Journal Section Research Article
Authors

Nur Özen 0000-0002-2332-3449

Leyla Abueid 0000-0002-7751-147X

Ahmet Yıldırım 0000-0001-5930-9756

Pınar Ülker 0000-0003-1772-5641

Filiz Basralı 0000-0002-6692-7779

Project Number Akdeniz University Scientific Research Projects Coordination Unit: TDK-2018-4057
Submission Date July 31, 2025
Acceptance Date December 5, 2025
Publication Date December 22, 2025
Published in Issue Year 2025 Volume: 50 Issue: 4

Cite

MLA Özen, Nur et al. “Effect of Swimming Exercise on Angiotensin-(1–7)-Mediated Aortic Dilation Responses in the Nitric Oxide Synthase Inhibition-Induced Hypertensive Rats”. Cukurova Medical Journal, vol. 50, no. 4, 2025, pp. 1092-0, doi:10.17826/cumj.1753982.