Downregulation of cystathionine γ lyase and endothelial nitric oxide synthase and reduced responsiveness of α_1A adrenergic receptors in the kidneys of left ventricular hypertrophied Wistar Kyoto rats

Authors: ASHFAQ AHMAD, MUNAVVAR ABDUL SATTAR, HASSAAN ANWER RATHORE, SAFIA AKHTAR KHAN, NOR AZIZAN ABDULLAH, EDWARD JAMES JOHNS

Abstract: This article explores the relationship between the renal expression of cystathionine gamma lyase (CSE) and endothelial nitric oxide synthase (eNOS) and the responsiveness of α_1A adrenergic receptors in the renal vasculature following left ventricular hypertrophy (LVH) in rats. LVH was established by administering isoprenaline (5 mg/kg, 5 injections subcutaneously, 72 h apart) with 62 mg/L caffeine in drinking water for 2 weeks. Renal vasoconstrictor responses were measured using local administration of adrenergic agonists noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) and the selective α_1A adrenergic antagonist 5-methylurapidil (5-MeU). Mean arterial blood pressure was higher (144 ± 9 vs. 116 ± 4 mmHg) and renal cortical blood perfusion was lower in the LVH group (102 ± 5 vs. 157 ± 19 bpu) compared to the control group (P < 0.05). There was a 68% downregulation of mRNA for renal CSE and 79% for eNOS in the LVH group compared to the control group (taken as 100%) (P < 0.05). The high dose of 5-MeU attenuated the vasoconstrictor responses to NA by 33%, PE by 44%, and ME by 43% in the LVH group compared to the same dose in the control group. The reductions in basal renal cortical perfusion and α_1A adrenergic receptor vasoconstrictor responses in LVH were associated with the downregulation of the CSE/H2S and eNOS/NO pathways.

Keywords: Adrenergic receptors, isoprenaline, caffeine, left ventricular hypertrophy

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