Interaction between the renin angiotensin system and a1-adrenergic receptors at the renal resistance vessels in diabetes mellitus and hypertension
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Date
2007-06
Authors
Dewa, Aidiahmad
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Abstract
a1-adrenoceptors and angiotensin type 1 (AT1) receptor subtype play important roles in
the regulation of renal haemodynamic at the level of renal resistance vasculature. It is
known that diabetes mellitus could damage the peripheral blood vessels and nerves,
and is worsen by hypertensive state. This study was designed to examine the
functional role of a,-adrenoceptor subtypes and AT1-receptor at the renal vasculature
resistance in diabetes mellitus, hypertension and combination of both pathological
states, and any possible intrarenal functional interaction between the a1-adrenoceptors
and local renin-angiotensin systems. Normotensive WKY and SHR rats were utilized.
Diabetes mellitus was induced by a single dose of streptozotocin at 55 mg.kg·1
intraperitoneally. Body weight, water intake, urine output, plasma glucose and sodium
levels, and urinary sodium excretion were monitored. During the acute study, the rats
were anaesthetized with pentobarbitone sodium at 60 mg.kg-1 intraperitoneally.
Following tracheostomy to allow facilitated breathing, the left jugular vein and the right
carotid artery were cannulated for continuous infusion of saline and measurement of
the mean arterial blood pressure, respectively. Having performed a midline abdominal
incision, the internal abdominal organs were carefully displaced to the right side to
expose the left kidney. An electromagnetic flow probe was placed on the renal artery
for renal blood flow (RBF) measurement. Bipolar electrodes were used to stimulate
renal nerve. Upon completion of surgery, 2 ml of saline was given intravenously as a
primer, and one hour period of stabilization was observed. Reductions in RBF to
electrical stimulation (1, 2, 4, 6, 8, and 10 Hz at 15V, 2 ms), bolus doses of
phenylephrine (0.25, 0.50, 1.00, and 2.00 11g), methoxamine (0.50, 1.00, 2.00, and 4.00
11g) and angiotensin II (2.50, 5.00, 10.00, and 20.00 ng) were determined in the
presence of 5-methylurapidil (5.00 and 10.00 J.!g.kg-1 plus 1.25 and 2.50 J.!g.kg·1.hr·
chloroethylclonidine (5.00 and 10.00 J.!g.kg-1 plus 1.25 and 2.50 J.!g.kg·1.hr'\ BMY7378
(100.00 and 200.00 J.!g.kg-1 plus 25.00 and 50.00 J.!g.kg·1.hr'\ amlodipine (200.00 and
400.00 J.!g.kg-1 plus 50.00 and 100.00 J.!g.kg·1.hr'1), perindopril (0.20 mg.kg-1
) and
losartan (10.00 mg.kg·\ and mean arterial pressure (MAP) were monitored. Data,
means.±. s.e.m., were analyzed with one- and two-ways analysis of variance followed
by Bonferroni post hoc with the significance level of 5%. Significant reductions in body
weight, higher water intake and urine output were observed in diabetic as compared to
nondiabetic animals. Baseline values of MAP remained consistent throughout study
except in few groups, whereas the RBF values remained unaltered in all experimental
groups. From the renal vasoconstrictor responses, the a1A-adrenoceptor subtype and
postsynaptic AT1-receptors are functionally important in mediating the vasoconstriction
of the resistance vessels in nondiabetic and diabetic WKY and SHR rats. Functionality
of a18- and a10-adrenoceptor subtypes and circulating Ang II were greatly influenced by
the pathological states of diabetes mellitus and hypertension. In nondiabetic WKY, the
interaction between the renin angiotensin system and a1-adrenoceptor subtypes
occurred mainly through a, 8-adrenoceptor subtype and AT1-receptor, and under the
influence of diabetic and hypertensive conditions, the a1A- and a10-adrenoceptor
subtypes became increasingly involved in the interaction. Circulating Ang II exerted
greater effects on the responses mediated by a,-adrenergic receptors than by AT,receptors.
In conclusion, intrarenal interaction between the a1-adrenergic receptors and
AT1-receptor exists at the level of renal resistance vessels, and this is greatly
influenced by the pathological conditions of diabetes mellitus and hypertension.
Description
Keywords
Renin angiotensin system , a1-adrenergic receptors