Sains Malaysiana 51(7)(2022): 2147-2157

http://doi.org/10.17576/jsm-2022-5107-17

Repeated Administration of Low Dose Isoprenaline on the Rat’s Cardiovascular System

(Administrasi Berulang Isoprenalina Dos Rendah pada Sistem Kardiovaskular Tikus)

RAJASEGAR ANAMALLEY^1,4, LOGESWARY RAJASSAGERAN¹, YASAASWINI APPAROO¹, MUHAMMAD HAFFIZ JAURI³, YUSOF KAMISAH², NURHANAN MURNI YUNOS³ & SATIRAH ZAINALABIDIN^1,*

¹Programme of Biomedical Science, Centre of Toxicology and Health Risk Study (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

²Department of Pharmacology, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000 Cheras Kuala Lumpur, Federal Territory, Malaysia

³Natural Products Division, Forest Research Institute Malaysia (FRIM), 52109 Kepong, Selangor Darul Ehsan, Malaysia

⁴Faculty of Health and Life Sciences, Management and Science University, University Drive, off Persiaran Olahraga, 40100 Shah Alam, Selangor Darul Ehsan, Malaysia

Received: 21 September 2021/Accepted: 28 December 2021

Abstract

Isoprenaline (ISO) at high doses can cause severe stress to myocardium resulting in an infarct-like necrosis in rats. However, its effects at repeatedly low dose exposure on heart, kidney and aorta are still unclear. Hence, this study was aimed to investigate the effects of repeated administration of low dose ISO on the organs in rats by using Langendorff-perfused isolated hearts, ELISA kits, qPCR and histopathology techniques. Male Wistar rats (n=24) were randomly divided into three groups which were given 5 or 10 mg/kg/day of ISO (ISO 5 and ISO 10, respectively), or normal saline (control) subcutaneously for 14 days. Blood pressure was recorded at day-0, 7 and 14. Heart, aorta, kidneys, and blood were then collected. ISO at both doses significantly increased the heart weight and blood pressure (p<0.05), while the heart rate was significantly decreased (p<0.05). ISO also increased serum troponin and NT-pro-BNP, and decreased vascular relaxation dose-dependently. Group ISO 10 showed significantly increased cardiomyocyte area and cardiac collagen content, as well as reduced serum nitrite (p<0.05). However, ISO at both doses did not affect the cardiac mechanical function, renal oxidative stress, inflammation, as well as renal gene expressions of angiotensin-converting enzyme and angiotensin II type 1 receptor. In conclusion, repeated low dose of ISO significantly causes myocardial injury and reduces vascular function in rats. The findings imply that this rat model could be a suitable model of heart injury without the complication of renal injury.

Keywords: β-adrenoceptor; cardiac hypertrophy; fibrosis; isoprenaline; vascular fibrosis

Abstrak

Aruhan isoprenalina (ISO) pada dos tinggi boleh menyebabkan tekanan yang teruk pada miokardium lalu mengakibatkan nekrosis pada jantung tikus. Walau bagaimanapun, kesan pendedahan pada dos rendah berulangan pada jantung, ginjal dan aorta masih belum jelas diketahui. Oleh itu, penyelidikan ini bertujuan untuk mengkaji kesan pemberian ISO dos rendah secara berulangan pada organ-organ tikus dengan menggunakan teknik jantung terpisah yang diperfusi Langendorff, kit ELISA, qPCR dan histopatologi. Tikus Wistar jantan (n=24) dibahagikan secara rawak kepada tiga kumpulan iaitu 5 atau 10 mg/kg/hari suntikan ISO (ISO 5 dan ISO 10), atau salina normal (kawalan) secara subkutan selama 14 hari. Tekanan darah diambil pada hari ke-0, 7 dan 14. Organ jantung, aorta, ginjal dan darah kemudian dibedah. Hasil kajian mendapati aruhan ISO pada kedua-dua dos tersebut telah meningkatkan berat jantung dan tekanan darah dengan ketara (p<0.05), sementara kadar denyutan jantung pula menurun dengan ketara (p<0.05). ISO juga meningkatkan troponin serum dan NT-pro-BNP dan penurunan relaksasi vaskular. Hanya ISO 10 berupaya mengaruh peningkatan kawasan  kardiomiosit dan jumlah kolagen jantung, serta penurunan nitrit serum (p<0.05). ISO pada kedua-dua dos tersebut tidak pula mempengaruhi fungsi mekanikal jantung, tekanan oksidatif ginjal, keradangan, serta ekspresi gen penukaran enzim angiotensin dan reseptor angiotensin II Jenis 1. Kesimpulannya, aruhan dos rendah ISO yang berulang menyebabkan kecederaan miokardium dan mengurangkan fungsi vaskular pada tikus. Hasil kajian ini menunjukkan bahawa model tikus ini boleh dijadikan sebagai satu model tikus dengan kegagalan jantung tanpa sebarang komplikasi pada buah pinggang.

Kata kunci: β adrenoseptor; fibrosis salur darah; kardiak hipertrofi; fibrosis; isoprenalina

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^*Corresponding author; email: satirah@ukm.edu.my