The Antihypertensive Effect of Irbesartan in Spontaneously Hypertensive Rats is Associated with Improvement of the Leptin-adiponectin Imbalance

Overview

Journal Adipocyte

Specialties Cell Biology
Endocrinology
Physiology

Date 2021 Feb 11

PMID 33570444

Citations 1

Authors

Junting Weng

Min Chen

Rongjie Guo

Shuzhen Yang

Danjuan Liu

Dexiang Fang

Affiliations

Soon will be listed here.

Abstract

Objective: This study aimed to investigate whether the antihypertensive effect of irbesartan (IRB) in spontaneously hypertensive rats (SHR) was achieved through improvement of insulin resistance and adjustment of the LPN-APN imbalance.

Methods: SHR rats were divided into SHAM, SHR-A and SHR-I group(8 per group). Homologous Wistar-Kyoto (WKY) rats were used as control group (WKY).The SHR-I group received 30 mg/kg/d IRB, the SHR-A group received 2.5 mg/kg AML. After 8 weeks, systolic blood pressure (SBP) was measured. The concentrations of blood glucose, insulin, LPN and APN were detected. Rat epididymal adipose tissues were collected to analyze the mRNA expression levels ofepididymal LPN and APN using reverse transcription-polymerase chain reaction. In addition, the LPN/APN ratio was calculated. Results:SBP, homeostasis model assessment of insulin resistance (HOMA-IR), LPN concentration, adipose LPN mRNA expression level, and the LPN/APN ratio increased (<0.05) and APN concentration and adipose APN mRNA expression level decreased (<0.05) in SHR rats.IRB decreased SBP, HOMA-IR, serum LPN, adipose LPN mRNA expression, and the LPN/APN ratio and increased serum APN and adipose APN mRNA expression.

Conclusion: The antihypertensive effect of IRB in SHR rats was associated with its improvement of insulin resistance and correction of the LPN-APN imbalance. ANOVA, one-way analysis of variance; SHR, Spontaneously hypertensive rats; WKY, Wistar kyoto rats; IRB, Irbesartan; AML, Amlodipine; LPN, Leptin; APN, Adiponectin; Ang-II, AngiotensinⅡ; HOMA-IR, Homoeostasis model assessment-insulin resistance; SBP, Systolic blood pressure; RT-PCR, Reverse transcription polymerase chain reaction; ARB, AngiotensinⅡreceptor blocker.

Citing Articles

Effect of administration of low-dose irbesartan and hydrochlorothiazide combined with levamlodipine at different times on the circadian rhythm of blood pressure and the levels of MMPs and TIMPs in non-dipper patients with grade 1 and 2 hypertension.

Yan P, Luo Y, Zhang J, Liu H, Chen J, Wang J J Clin Hypertens (Greenwich). 2023; 25(2):137-145.

PMID: 36639984 PMC: 9903188. DOI: 10.1111/jch.14630.

References

Guo X, Cheng S, Taylor K, Cui J, Hughes R, Quinones M . Hypertension genes are genetic markers for insulin sensitivity and resistance. Hypertension. 2005; 45(4):799-803. DOI: 10.1161/01.HYP.0000154786.17416.ea. View

Isezuo S . The metabolic syndrome: Review of current concepts. Niger Postgrad Med J. 2007; 13(3):247-55. View

Quilliot D, Bohme P, Zannad F, Ziegler O . Sympathetic-leptin relationship in obesity: effect of weight loss. Metabolism. 2008; 57(4):555-62. DOI: 10.1016/j.metabol.2007.11.020. View

Adejumo E, Adejumo O, Azenabor A, Ekun A, Enitan S, Adebola O . Leptin: Adiponectin ratio discriminated the risk of metabolic syndrome better than adiponectin and leptin in Southwest Nigeria. Diabetes Metab Syndr. 2019; 13(3):1845-1849. DOI: 10.1016/j.dsx.2019.04.008. View

Zeidan A, Purdham D, Rajapurohitam V, Javadov S, Chakrabarti S, Karmazyn M . Leptin induces vascular smooth muscle cell hypertrophy through angiotensin II- and endothelin-1-dependent mechanisms and mediates stretch-induced hypertrophy. J Pharmacol Exp Ther. 2005; 315(3):1075-84. DOI: 10.1124/jpet.105.091561. View

Julius S, Kjeldsen S, Weber M, Brunner H, Ekman S, Hansson L . Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004; 363(9426):2022-31. DOI: 10.1016/S0140-6736(04)16451-9. View

Vega G, Grundy S . Metabolic risk susceptibility in men is partially related to adiponectin/leptin ratio. J Obes. 2013; 2013:409679. PMC: 3606776. DOI: 10.1155/2013/409679. View

Lindholm L, Ibsen H, Dahlof B, Devereux R, Beevers G, de Faire U . Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002; 359(9311):1004-10. DOI: 10.1016/S0140-6736(02)08090-X. View

Cohen S, Halaas J, Friedman J, Chait B, Bennett L, Chang D . Human leptin characterization. Nature. 1996; 382(6592):589. DOI: 10.1038/382589a0. View

10.

Cassis L, English V, Bharadwaj K, Boustany C . Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes. Endocrinology. 2003; 145(1):169-74. DOI: 10.1210/en.2003-0767. View

11.

Lindberg S, Jensen J, Bjerre M, Frystyk J, Flyvbjerg A, Jeppesen J . Low adiponectin levels at baseline and decreasing adiponectin levels over 10 years of follow-up predict risk of the metabolic syndrome. Diabetes Metab. 2016; 43(2):134-139. DOI: 10.1016/j.diabet.2016.07.027. View

12.

Lee K, Shin D . Prospective Associations of Serum Adiponectin, Leptin, and Leptin-Adiponectin Ratio with Incidence of Metabolic Syndrome: The Korean Genome and Epidemiology Study. Int J Environ Res Public Health. 2020; 17(9). PMC: 7246697. DOI: 10.3390/ijerph17093287. View

13.

Bogan J, Lodish H . Two compartments for insulin-stimulated exocytosis in 3T3-L1 adipocytes defined by endogenous ACRP30 and GLUT4. J Cell Biol. 1999; 146(3):609-20. PMC: 2150549. DOI: 10.1083/jcb.146.3.609. View

14.

Leung Y, Kwan C . Dual vascular effects of leptin via endothelium: hypothesis and perspective. Chin J Physiol. 2008; 51(1):1-6. View

15.

Cusin I, Sainsbury A, Doyle P, Rohner-Jeanrenaud F, Jeanrenaud B . The ob gene and insulin. A relationship leading to clues to the understanding of obesity. Diabetes. 1995; 44(12):1467-70. DOI: 10.2337/diab.44.12.1467. View

16.

Borghi F, Seva-Pessoa B, Grassi-Kassisse D . The adipose tissue and the involvement of the renin-angiotensin-aldosterone system in cardiometabolic syndrome. Cell Tissue Res. 2016; 366(3):543-548. DOI: 10.1007/s00441-016-2515-6. View

17.

Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28(7):412-9. DOI: 10.1007/BF00280883. View

18.

Furuhashi M, Ura N, Higashiura K, Murakami H, Tanaka M, Moniwa N . Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. Hypertension. 2003; 42(1):76-81. DOI: 10.1161/01.HYP.0000078490.59735.6E. View

19.

Campfield L, Smith F, Guisez Y, Devos R, Burn P . Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995; 269(5223):546-9. DOI: 10.1126/science.7624778. View