The Control Of Renal Haemodynamics By The Adrenergic Nervous System In A Combined State Of Hypertension, Heart Failure And Diabetes- Role Of Ul- Adrenoceptor Subtypes.

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Date
2003-04
Authors
Syed Abbas, Syed Atif
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Abstract
au'\.- adrenoceptor subtypes primarily mediate adrenergically induced constriction of renal vasculature. Type I diabetes is associated with autonomic neuropathies which cause a defective autonomic control of major organs. The present study was designed to determine the functional Ul- adrenoceptor subtype in the renal vasculature at the level of the arterioles of the SHR. and SD rats with cardiac failure and diabetes. Diabetes was induced by a single dose of streptozotocin (SSmg/kg IP). Cardiac failure was induced by the combined treatment of caffeine (40mg/kg) and isoprenaline (Smg/kg) for seven days. On day eight the rats were used for acute the study. The animal was anaesthetised with pentobarbitone sodium (60mg/kg IP). After tracheotomy, the left jugular vein and carotid artery were cannulated to allow the continuous infusion of anaesthesia and to measure the arterial blood pressure respectively. The left kidney was exposed by carefulIy moving the abdominal contents to right side following a midline abdominal incision. The renal artery was cleared and an electromagnetic flow probe was plat:ed :m it to determine the renal blood flow (RBF). The ll;ft iliac artery was cannulated such that the beveled tip of cannula faced the renal artery for the infusion of saline and all drugs close renal arterially. The renal nerves were identified, isolated and placed on bipolar electrodes for electrical stimulations. Upon the completion of surgery 2ml of saline was injected intravenously as primer. The reduction in REF to electrical nerve stimulation (at I, 2, 4, 6, 8 and 10Hz at 15 V and 2ms), bolus doses of noradrenaline (25, 50, 100 and 200 ng), phenylephrine (0.25,0.5, 1.0 and 2.0 Ilg) and methoxamine (1,2,3 and 4 Ilg) were determined before and after bolus doses of amlodipine (200 and 400 ~lg/kg plus 50 and I 00 ~lg/kg/h), 5 methylurapidil (5 and 10 Ilg/kg plus 125 and 25 pg/kglh), chlorethylclonidine (5 and 10 J.1g/kg plus 1.25 and 2.5 J.1g/kg/h) and BMY7378 (100 and 200 J.1g/kg plus 25 and 50 J.1g/kg/h). Data, means ± s.e.m were compared with 2 way ANOYA followed by Bonferroni post hoc with the significance level of 5%. The results obtained indicated that the renal vasoconstrictor responses in ths model were attenuated mainly by amlodipine, 5 methylurapidil and BMY73 78 but not by chlorethylclonidine. Administration of chlorethylclonidine did not show a significant reduction in methoxamine induced renal vasoconstriction in cardiac failure SHR and SO rats with and without diabetes. This supported the view that alA- adrenoceptors are involved in renal vasculature of cardiac failure and diabetes induced SO and SHR. However, in SHR with cardiac failure and diabetes, chlorethylclonidine resulted In minor non-significant reduction In vasoconstrictor responses induced by methoxamine. The possible explanation for this observation is that there: may be a complex interaction between the subtypes of adrenoceptors in cardiac failure as well as diabetes induced SHR. These findings supported that differences in al- adrenoceptor populations and distribution in blood vessels are dependent on the pathological state. The findings from this study also suggest that the alA and UID- adrenoceptors mediate the adrenergically induced renal vasoconstrictor responses in cardiac failure SO and SHR with and without diabetes.
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Type I diabetes is associated with autonomic neuropathies , which cause a defective autonomic control of major organs.
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