Functional contribution of α_1D-adrenoceptors in the renal vasculature of left ventricular hypertrophy induced with isoprenaline and caffeine in Wistar–Kyoto rats

Abstract

This study investigated the role of α1D-adrenoceptor in the modulation of renal haemodynamics in rats with left ventricular hypertrophy (LVH). LVH was established in Wistar-Kyoto (WKY) rats with isoprenaline (5.0 mg · (kg body mass)(-1), by subcutaneous injection every 72 h) and caffeine (62 mg · L(-1) in drinking water, daily for 14 days). Renal vasoconstrictor responses were measured for noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) before and immediately after low or high dose intrarenal infusions of BMY 7378, a selective α1D-adrenoceptor blocker. The rats with LVH had higher mean arterial blood pressure and circulating NA levels, but lower renal cortical blood perfusion compared with the control group (all P < 0.05). In the LVH group, the magnitude of the renal vasoconstrictor response to ME was blunted, but not the response to NA or PE (P < 0.05), compared with the control group (LVH vs. C, 38% vs. 50%). The magnitude of the drop in the vasoconstrictor responses to NA, PE, and ME in the presence of a higher dose of BMY 7378 was significantly greater in the LVH group compared with the control group (LVH vs. C, 45% vs. 25% for NA, 52% vs. 33% for PE, 66% vs. 53% for ME, all P < 0.05). These findings indicate an impaired renal vasoconstrictor response to adrenergic agonists during LVH. In addition, the α1D-adrenoceptor subtype plays a key role in the modulation of vascular responses in this diseased state.

Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol–Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats

“…Each group comprised: Control, LVH, Control-H 2 S and LVH-H 2 S (n = 6 rats per group) for the acute studies while same groups for the cardiac CSE mRNAs expression studies in which each group consists of 3 animals and each animal has triplicate so total number of replicate were 9 in one group (n = 9). LVH was induced by the administration of 5 subcutaneous injections of isoprenaline of 5mg/kg at 72 h intervals with caffeine 62mg/L in the drinking water for a period of 2 weeks as previously reported [ 32 , 33 ] but with minor modification as reported [ 30 ]. NaHS (H 2 S donor) was administered via an intra-peritoneal injection of NaHS (56μM) at the same time each day for 5 weeks [ 13 ].…”

“…A tail vein blood sample was taken on the final day and centrifuged at 5000rpm for 10 minutes [ 30 ]. The measurement of H 2 S in the heart tissue was followed as previously reported [ 38 ].…”

“…Plasma NA levels were measured on day 35 as reported [ 30 ]. Measurement of plasma NA concentration required 50 μL of plasma by processed following the instructions and using ELISA kit purchased from LaborDiagnostika Nord GmbH & Co. KG, Nordhorn, Germany.…”

“…After the completion of the ECG recording, the acute experiment was performed following previously reported procedures [ 30 , 44 , 45 ]. The trachea was exposed by a midline neck incision and a cannula inserted to provide ease of ventilation throughout the experiment.…”

“…Increased levels of vasoconstrictors, such as Ang II in a fructose fed model of LVH [ 27 ] and NA in isoprenaline/caffeine model have been reported [ 28 – 30 ]. However, the status of these vasoconstrictors in response to up regulation of the CSE/H 2 S pathway is unexplored.…”