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.
Description
Keywords
Type I diabetes is associated with autonomic neuropathies , which cause a defective autonomic control of major organs.