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Up regulation of endothelial nitric oxide synthase and nitric oxide in the kidney enhances the blunted responses of α 1D adrenoreceptors in the kidney of rats with left ventricular hypertrophy
Author(s) -
Rathore Hassaan Anwer,
Sattar Munavvar Zubaid Abdul,
Ahmad Ashfaq,
Johns Edward J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1005.1
Subject(s) - medicine , endocrinology , enos , left ventricular hypertrophy , nitric oxide , nitric oxide synthase , chemistry , methoxamine , kidney , saline , blood pressure , receptor , agonist
The functional contribution of α 1D ‐adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of left ventricular hypertrophy (LVH) rats was studied in the presence of exogenously administered L‐arginine. LVH was induced by isoprenaline administration (5mg, S/C, every 72 hours for 2 weeks) and caffeine in drinking water (62mg/L) for 2 weeks while NO (L‐arginine, 1.25g/L in drinking water) was given for 5 weeks. The responsiveness of α 1D to exogenous noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) in the absence and presence of BMY 7378 was studied under pentobarbitone sodium 60mg/kg i.p in accordance to AECUSM approval. The expression of endothelial nitric oxide (eNOS) mRNA was quantified by using real time polymerase chain reaction (qPCR) and an up regulation of eNOS mRNA in LVH‐NO group compared to LVH group (1.54 vs. 0.21) occurred. The base line renal cortical blood perfusion (RCBP) significantly increased 44% (P<0.05) in LVH‐NO compared to LVH. The responsiveness of α 1D adrenergic receptor to NA in saline, low dose and high dose phases of BMY7378 of LVH‐NO increased by 65%,55 % and 77 % respectively when compared to same phases of LVH. The responsiveness of α 1D adrenergic receptor to PE in saline, low dose and high dose phases of BMY7378 of LVH‐NO increased by 83%, 104 % and 131 % respectively when compared to same phases of LVH. Similarly responsiveness of α 1D adrenergic receptor to ME in saline, low dose and high dose phases of BMY7378 of LVH‐NO increased by 72%, 128 % and 277 % respectively when compared to same phases of LVH. Treatment with NO not only increased the attenuated baseline of renal cortical blood perfusion in LVH but also augmented the blunted responsiveness of α 1D ‐adrenoceptor subtypes in the kidney of rats with LVH via upregulation of eNOS/NO pathway. Support or Funding Information These experiments were funded by a Fundamental research Grant number 203/PFARMASI/6711452 awarded by the Ministry of Science, Technology & Innovation, Malaysia (MOSTI, Malaysia). 1eNOS in kidney2Vasoconstrictive responses of noradrenaline in the presence of BMY73783Vasoconstrictive responses of phenylephrine in the presence of BMY73784Vasoconstrictive responses of methoxamine in the presence of BMY73785Baseline renal cortical blood perfusion