The Effect of Chronic Angiotensin (1–7) Treatment on Functional Responses of Isolated Resistance Arteries in Streptozotocin-Induced Diabetic Rats

IF 2.7 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2026-07-14 DOI:10.1111/fcp.70107

Esra Akcabag, Ikbal Ozen Kucukcetin, Gul Ozbey, Sebahat Ozdem, Sadi S. Ozdem

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引用次数: 0

Abstract

Cardiovascular complications of diabetes mellitus (DM) are responsible for morbidity and mortality in DM patients. Recent evidence highlights the pathophysiological role of the renin-angiotensin-aldosterone system in DM. This study determined whether chronic angiotensin (1–7) (Ang (1–7); 576 μg/kg, s.c., 4 weeks) treatment improves vascular reactivity in mesenteric small resistance arteries of streptozotocin-induced diabetic rats using a wire myograph system and to investigate the underlying mechanisms. Increased sensitivity to vasoconstrictors and decreased responses to endothelium-dependent vasodilators in diabetic rats compared to control rats were partially reversed by Ang (1–7) treatment. Nω-nitro-L-arginine methyl ester (L-NAME, 10⁻⁴ M) incubation significantly decreased vasorelaxant responses to acetylcholine (ACH, 10⁻¹⁰–10⁻⁵ M) in all groups except the diabetic group. Superoxide dismutase (SOD, 50 U/mL) incubation produced significant increases in vasorelaxant responses to ACH only in the diabetic groups. Glibenclamide (10⁻⁵ M), 4-aminopyridine (4-AP, 5 mM), indomethacin (INDO, 10⁻⁵ M), or catalase (CAT, 200 U/mL) incubations did not alter ACH responses in any experimental groups, whereas charybdotoxin (ChTX, 10⁻⁷ M) or apamin (APA, 10⁻⁷ M) produced significant decreases in ACH-induced vasorelaxation, similar in extent in the control and diabetic rats. Following co-incubation with L-NAME and INDO, ACH-induced vasorelaxation in 30 mM KCl pre-contracted arterial rings did not differ significantly between the groups. These findings indicate that improved nitric oxide bioavailability and reduced superoxide activity contribute to the beneficial vascular effects of Ang (1–7) in diabetic rat resistance arteries. Further in vivo studies are warranted to clarify its therapeutic relevance.

Summary

Ang (1–7) improves vascular function in diabetic rat resistance arteries.
Treatment increases NO bioavailability and reduces oxidative stress.
Vasoconstrictor sensitivity is decreased, improving endothelium-dependent vasorelaxation.
Ang (1–7) restores vascular responses to endogenous vasoactive agents.
Findings suggest Ang (1–7) as a potential target for diabetes-related vascular issues.

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慢性血管紧张素（1-7）治疗对链脲佐菌素诱导糖尿病大鼠离体抵抗动脉功能反应的影响。

糖尿病（DM）的心血管并发症是糖尿病患者发病率和死亡率的主要原因。最近的证据强调了肾素-血管紧张素-醛固酮系统在糖尿病中的病理生理作用。本研究确定了慢性血管紧张素（1-7）(Ang (1-7)；576 μg/kg, s.c， 4周)治疗可改善链脲唑霉素诱导的糖尿病大鼠肠系膜小抵抗动脉的血管反应性，并探讨其潜在机制。与对照大鼠相比，糖尿病大鼠对血管收缩剂的敏感性增加，对内皮依赖性血管扩张剂的反应降低，但Ang（1-7）治疗部分逆转了这一现象。ω-硝基- l -精氨酸甲酯（L-NAME, 10-4 M）孵养显著降低除糖尿病组外各组对乙酰胆碱（ACH, 10-10-10-5 M）的血管松弛反应。超氧化物歧化酶（SOD, 50 U/mL）孵育仅在糖尿病组对乙酰胆碱的血管松弛反应显著增加。格列本脲（10-5 μ M）、4-氨基吡啶（4-AP, 5 μ M）、吲哚美辛（INDO, 10-5 μ M）或过氧化氢酶（CAT, 200 U/mL）在任何实验组中均未改变乙酰胆碱反应，而白肉毒素（ChTX, 10-7 μ M）或木瓜素（APA, 10-7 μ M）显著降低乙酰胆碱诱导的血管松弛，其程度与对照组和糖尿病大鼠相似。与L-NAME和INDO共孵育后，30 mM KCl预收缩动脉环中ach诱导的血管松弛在组间无显著差异。这些发现表明，提高一氧化氮的生物利用度和降低超氧化物活性有助于Ang（1-7）在糖尿病大鼠动脉中的有益血管作用。需要进一步的体内研究来阐明其治疗相关性。摘要：Ang（1-7）改善糖尿病大鼠动脉血管功能。治疗增加NO的生物利用度，减少氧化应激。血管收缩剂敏感性降低，改善内皮依赖性血管松弛。Ang（1-7）恢复血管对内源性血管活性药物的反应。研究结果表明，Ang（1-7）是糖尿病相关血管问题的潜在靶点。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.