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Introduction
The sympathetic nervous system plays an important role
in the control of renal
hemodynamics[1,2]. In renal vasculature,
the catecholamines released from the nerve terminals
activate G protein-coupled cell surface adrenoceptors present
on the cell surface and cause
contraction[3,2]. Three subtypes of
α1-adrenoceptor subtypes, namely
α1A, α1B,
and α1D, have been documented based on pharmacological and
cloning studies[4_7]. These subtypes are closely related to each
other in terms of amino acid sequence, ligand affinity, and
also with respect to irreversible blockade by certain
alkylating agents[8]. Several in
vivo and in vitro studies have revealed that, functionally,
α1-adrenoceptors predominate in the renal
vasculature[9_11]. In rat renal vasculature, all of the
3 subtypes of α1-adrenoceptors have been shown to
mediate catecholamine-induced
constriction[2,9_11] along with a dominant role of the
α1A-subtype[10,11]. Some reports have
also shown the functional involvement of other subtypes,
such as α1D-adrenoceptors, in renal
vasculature[2,12_14].
The α1B-adrenoceptors are also involved in mediating
vasoconstrictions as observed in in vitro studies with the
mesenteric resistance artery and tail artery of
rats[15,16]. This subtype is also present in the renal resistance vessel and
receptor binding. The RNase protection assay revealed the
expression of α1B-adrenoceptors in the renal microvessels of
Wistar Kyoto and spontaneously hypertensive rats.
However, there is no report on the functional contribution of
this subtype in modulating adrenergically-induced renal
vasoconstriction except reports on its minor involvement. A
minor functional involvement of α1B-adrenoceptors in
mediating renal vasoconstriction is reported in rats with some
altered physiological or pathological states. In diabetes,
hypertensive diabetes, heart failure, and renal failure, a
minor involvement of this receptor subtype has been reported
in mediating renal adrenergic responsiveness in
rats[4,17,18]. Some pathological states are indeed found to influence the
functional contribution of α1-adrenoceptors, including the
α1B-subtype, in rat renal
vasculature[14,18,19]. However, there is still an apparent paucity of information on the functional
involvement of α1B-adrenoceptors in modulating renal
vasoconstrictions that could strengthen this view. It is
particularly true in terms of further study of this interesting
observation in some other pathological states.
The present study investigated the influence of some
pathological states with renal impairment on the functional
presence of α1B-adrenoceptors in terms of its selective
affinity for chloroethylclonidine. The results of this study will
provide further evidence on the pathological
state-dependent involvement of α1B-adrenoceptors in modulating
adrenergically-induced renal vascular tone in rats.
Methods and materials
Animals Male Wistar Kyoto and spontaneously
hypertensive rats with (body weight range: 250_300 g, 267±8.3 g)
were supplied with commercial rat chow and water
ad libitum. They were maintained in the Animal Care Facility,
Universiti Sains Malaysia, Penang, Malaysia. Animal
handling and all animal procedures were approved by the
Animal Ethics Committee, Universiti Sains Malaysia. The
animals were randomly divided into 6 groups. Groups 1 and 2
(n=5_9 rats in each group) were normal and renal failure
Wistar Kyoto rats, groups 3 and 4 (n=5_9 rats in each
group) were normal and renal failure spontaneously
hypertensive rats, and groups 5 and 6 (n=5_9 rats in each group)
were rats with experimental early diabetic nephropathy and
the non-diabetic nephropathy control group, respectively.
Induction of renal failure and physiological data
collection The animals were caged individually in custom-built
stainless steel metabolic cages and acclimatized for at least
3 d before the induction of renal failure with cisplatin.
Baseline physiological data (body weight, 24 h water intake,
and urine output) were recorded. The animals fasted for at
least 12 h and on the following day received a single
intraperitoneal injection of cisplatin (55
mg/kg)[20_22]. Further physiological data were collected on every alternate day
until the animals were used in the acute renal hemodynamic
study on d 7. Tail vein blood samples were collected on d 0
and 7, and plasma were separated and frozen (-70
oC) until analyzed for creatinine and sodium using
spectrophotometry and flame photometry, respectively. The kidney index
was calculated as 100×kidney weight/body
weight[23_25]. The kidney tissues were preserved in 10% formalin for the
histological examinations using conventional hematoxylin and
eosin staining followed by the analysis of micrographs
(Leica image analyzing system, London, UK). Apart from
the examinations of the kidney index and histological study
of the kidney, renal failure and impairment of renal
functions in these rats were assessed from plasma creatinine,
creatinine clearance, fractional excretion of sodium, and
the glomerular filtration rate.
Preparation of experimental early diabetic
nephropathy rats and physiological data collection
The rats with experimental early diabetic nephropathy were
developed using spontaneously hypertensive rats by a slightly
modified method described earlier by several
researchers[25,26_28]. In this approach, the spontaneously
hypertensive rats were treated with a single intraperitoneal injection
(55 mg/kg) of streptozotocin after 12_16 h of fasting. On d 3
of post-streptozotocin injection fasting
(>12 h), blood glucose was tested (between 9:00_9:30) to confirm the
diabetic state. Rats with a fasting blood glucose level of
>13.8 mmol/L were considered to be
diabetic[25,27,29_30]. The rats with
confirmed diabetes were then randomly allotted in different
experimental groups according to the experimental design.
Blood glucose was tested once per week over a period of 4
weeks to observe their glycemic status. Rat with blood
glucose less than 300 mg/dL (<13.8 mmol/L) were excluded from
the study[27,30].
Apart from elevated blood glucose, other physiological
changes, such as polyuria and a reduction in the body weight,
were also considered in selecting the diabetic animals. The
diabetic rats were kept for 28 d for weekly physiological data
collection and also for the development of changes in renal
functional parameters, such as creatinine clearance, fractional
excretion of sodium, glomerular filtration rate, and the
urinary albumin excretion rate. Creatinine and sodium in the
plasma and urine were measured using spectrophotometry
and flame photometry, respectively, and urinary albumin was
measured using ELISA[31]. Finally, on d 29 the rats were
used in the acute study for renal hemodynamic data
collection. After the hemodynamic study, the kidney
tissues were collected, the weight of the kidneys was recorded
for the determination of the kidney index (kidney
index=100×kidney weight/body weight), and the kidneys
were then preserved in 10% formalin for the histological
examinations.
Hemodynamic study
Surgical preparation of the animal The overnight
(¡Ý12 h)-fasted (with water ad libitum) rats were anaesthetized
with 60 mg/kg (ip) sodium pentobarbitone (Nembutal, CEVA
Sante Animale, Libourne, France). After a tracheostomy
with endotracheal cannula (PP240, Protex, Kent, England)
the carotid artery was cannulated (PE 50, Protex, England)
and connected to a pressure transducer (P23 ID Gould,
Statham Instruments, Oakland, CA, USA) coupled to a
computerized data acquisition system (PowerLab,
AD-Instruments, Sydney, NSW, Australia) for the continuous
measurement of the mean arterial blood pressure. The left
jugular vein was cannulated (PE 50, Protex, England) to
permit the infusion of maintenance doses of anesthesia.
The left kidney was exposed using a midline abdominal
incision. The renal artery was carefully cleared and fitted
with an electromagnetic flow probe (EP 100 series, Carolina
Medical Instruments, King, North Carolina, USA) that was
connected to an electromagnetic flow meter (Carolina
Medical Instruments, USA) for the continuous measurement of
renal blood flow. A cannula (PE 50, Protex, England) was
inserted via the iliac artery so that its beveled tip lay close to
the entrance of the renal artery to enable the exogenous
administration of adrenergic agonists and
antagonists[10,11]. The cannula was kept patent by the continuous infusion of
saline at a rate of 6
mL·kg-1·h-1. The renal nerves passing
from the coeliac and aortico-renal ganglia to the kidney were
isolated and carefully dissected for a short length and placed
on fine bipolar stainless steel wire electrodes. The
functionality of the renal nerves was tested by stimulating (Grass S
48 Stimulator, Grass Instruments, Quincy, MA, USA) them
at 15 V, 0.2 ms, and 1_10 Hz for 30 s to observe whether
blanching of the kidney occurred. At the end of the
experiment, the animals were euthanized by an overdose of anesthetic
(sodium pentobarbitone; Nembutal, CEVA Sante Animale,
France), and an autopsy was done followed by the disposal
of the animal carcasses in accordance with the guidelines of
the Animal Ethics Committee of the Universiti Sains Malaysia.
Experimental protocol The experiment was comprised
of 3 phases. In the first phase, saline was infused
continuously and intrarenally during which the renal nerves were
stimulated at increasing frequencies of 1, 2, 4, 6, 8, and 10 Hz
and then in the reverse order. Subsequently, graded bolus
doses of noradrenaline (25, 50,100, and 200 ng; Sanofi Winthrop,
Guildford, UK), phenylephrine (0.25, 0.5, 1, and 2
μg; Knoll, Nottingham , UK), and methoxamine (1, 2, 3, and 4
μg; Wellcome, London, UK) were administered in ascending and then
descending doses. After the first phase, a close intrarenal
administration of a bolus dose (5 μg/kg) of chloroethylclonidine (Sigma, St
Louis, MO, USA) was given followed by a continuous infusion
of 1.25
μg·kg-1·h-1. Twenty minutes later, the second set of
vasoconstriction experiments were carried out. In the last phase,
a bolus dose of 10 μg/kg chloroethylclonidine plus a
continuous infusion of 2.5
μg·kg-1·h-1 was administered. Twenty
minutes latter the last set of vasoconstriction experiments were
carried out as described earlier[10,11].
Renal vasoconstrictor responses The
vasoconstrictor responses were recorded as the percentage changes of
renal blood flow in relation to the baseline values during
graded frequencies of renal nerve stimulation and graded
doses of agonist administered. The responses were recorded
using a computerized data acquisition system (PowerLab,
ADInstruments, Australia).
Adrenergic agonist and antagonists
Chloroethyl-clonidine
(N-β-chloroethyl-N-methylamino-methyl-
clonidine), a selective antagonist of
α1B-adrenoceptors and the most widely used agent in characterizing
α1B-adreno-ceptors, was used in this study for characterizing the
functional involvement of α1B-adrenoceptors in mediating
adrenergically-induced renal vasoconstriction, and can
differentiate between α1A- and
α1B-adrenoceptor
subtypes[32]. Regarding the
α1-adrenoceptors, the effects of chloroethyl-clonidine
have been related to the alkylation and inactivation of the
a1-adrenoceptor subtypes as irreversible antagonist in the
order of sensitivity of the α1B
¡Ýα1D>>α1A-adreno-ceptor
subtypes[14,33]. Chloroethylclonidine was prepared in saline as
recommended by the manufacturer and kept as aliquots of
frozen stock and diluted prior to use.
The adrenergic agonists used were noradrenaline,
phenylephrine, and methoxamine. Noradrenaline is a mixed
agonist that acts on both the α1 and
α2-adrenoceptors; phenylephrine is a non-selective agonist of
α1-adrenoceptors with an ability to activate
α1A-, α1B-, and
α1D-adrenoceptor
subtypes[14]; and methoxamine is a relatively selective
α1A-adrenoceptor-subtype
agonist[13,14], but may activate
α1D-adrenoceptors as it does not exhibit selectivity between
α1A- and
α1D-adrenoceptors[13]. Noradrenaline, phenylephrine,
and methoxamine were prepared fresh in saline (150 mmol/L
NaCl) from frozen stocks daily prior to use.
Statistical analysis The renal blood flow responses caused
by renal nerve stimulation, noradrenaline,
phenylephrine, and methoxamine were taken as the average values caused by
each dose/frequency of adrenergic stimuli administered and
applied in ascending and descending orders. The overall
mean response for each dose or frequency was taken as
the average value of vasoconstrictor responses (drop in
renal blood flow) obtained at each level of frequency for
renal nerve stimulation and each dose of the adrenergic
agonists used. The data on the drop of renal blood flow
were expressed as the percentage drop on the renal blood
flow in relation to the basal values of renal blood flow
calculated at the beginning of the administration of each
stimulus (renal nerve stimulation and adrenergic agonists) used.
All data were expressed as mean percentage change±SEM
of renal vasoconstrictor responses elicited by all the
frequencies (renal nerve stimulation) and all the doses
(adrenergic agonists) and were compared between the
phases (saline, low dose of chloroethylclonidine, and high
dose of chloroethylclonidine-treated phases). In the renal
vasoconstriction experiments, two-way ANOVA was used
for the statistical analysis. For the analysis of the
physiological and other data, one-way ANOVA was used
followed by the Bonferroni post-hoc test (Superanova,
Abacus, Barkley CA, USA). The differences between the
means were considered significant at the 5% level. All
physiological and biochemical data (body weight, 24 h water
intake, 24 h urine output, plasma sodium, urinary sodium,
fractional excretion of sodium, creatinine clearance,
albumin excretion, glomerular filtration rate, and kidney index)
were analyzed using one-way ANOVA followed by the
Bonferroni post-hoc
test[8,10,11,14].
Results
General observations Renal failure was identified by
increased plasma creatinine, reduced creatinine clearance,
increased fractional excretion of sodium, reduced
glomerular filtration rate, and diuresis in the cisplatin-treated
renal failure rats (all P<0.01) as compared to the
non-cisplatin-treated non-renal failure animals (Table 1).
Moreover, there was a markedly increased (P<0.01)
kidney index (percentage of kidney weight to body weight)
and pronounced renal tubular damage in the renal failure as
compared to the non-renal failure rats (Table 1; Figure 1). In
the experimental early diabetic nephropathy rats, along with
marked hyperglycemia, there was increased serum creatinine,
creatinine clearance, urinary albumin excretion, glomerular
filtration rate (all P<0.01), moderately increased fractional
excretion of sodium (P>0.05), and an increased kidney index
(P<0.01). Unlike the renal failure rats, there was no adverse
tubular structural change in these rats as compared to the
non-diabetic nephropathy control rats (Table 1; Figure 1).
The baseline mean arterial blood pressure and renal blood
flow of all the experimental groups are presented in Table 2.
In the renal failure rats, renal blood flow was significantly
lower compared to the non-renal failure rats
(P<0.01). In the experimental early diabetic nephropathy rats, renal blood flow
was greater compared to the non-diabetic nephropathy rats.
However, this change in renal blood flow did not attain
statistical significance (P>0.05). In addition, the baseline mean
arterial blood pressure of these rats (renal failure and
experimental early diabetic nephropathy) was either lower or
unaltered (P>0.05) in the diseased rats when compared with the
non-renal failure or non-diabetic nephropathy rats.
Renal vasoconstrictor responses
Normal and renal failure Wistar Kyoto rats In the
case of renal nerve stimulation, the administration of
chloroethylclonidine produced an accentuation
(P<0.01) of renal nerve stimulation-induced renal vasoconstrictor
responses in the renal failure Wistar Kyoto rats; the
magnitudes of these changes were dose-dependent (Figure 2).
However, in normal Wistar Kyoto rats, chloroethylclonidine
did not cause any marked alterations in such responses.
The mixed adrenergic agonist noradrenaline-induced changes
were also unaltered by either doses of chloroethylclonidine
in these rats (Figure 2). In contrast, there was a marked
dose-dependent accentuation (P<0.01) of the
noradrenaline-induced renal vasoconstrictor responses in renal failure
Wistar Kyoto rats (Figure 2). In renal failure Wistar Kyoto
rats, phenylephrine and methoxamine-induced renal
vasoconstrictor responses were attenuated by
chloroethyl-clonidine (P<0.01). However, these responses in
non-renal failure Wistar Kyoto rats were unaltered by
chloroethyl-clonidine (Figure 2). The overall mean percentage changes
in the renal blood flow of renal failure and non-renal failure
Wistar Kyoto rats to different adrenergic stimuli are shown
in Table 3.
Spontaneously hypertensive and renal failure
spontaneously hypertensive rats Chloroethylclonidine
produced interesting results in renal failure spontaneously
hypertensive rats with a marked attenuation (by the low dose
of chloroethylclonidine) followed by accentuation (by the
high dose of chloroethylclonidine) of the renal nerve
stimulation-induced renal vasoconstrictor responses (all
P<
0.01). However, in normal spontaneously hypertensive rats,
chloroethylclonidine did not cause any meaningful alteration
in the renal nerve stimulation-induced renal
vasoconstrictor responses (Figure 3). In the case of noradrenaline-induced
vasoconstrictor responses, chloroethyl clonidine at both doses
did not canse any alteration (P>0.05)
in either of the experimental groups. In the spontaneously hypertensive rats,
neither dose of chloroethylclonidine showed any effect on
the phenylephrine and methoxamine-induced renal
vasoconstrictor responses (P>0.05). Interestingly, in the renal failure
spontaneously hypertensive rats, chloroethyl-clonidine in
its high dose caused enhancement of phenylephrine and
methoxamine-induced renal vasoconstrictor responses
(P< 0.01), while its low dose remained insensitive
(P>0.05; Figure 3). The overall mean percentage changes in the renal
blood flow of renal failure and non-renal failure
spontaneously hypertensive rats to different adrenergic stimuli are
shown in Table 3.
Rats with experimental early diabetic
nephropathy In these group of rats chloroethylclonidine accentuated (all
P<0.01) all the adrenergically-induced renal vasoconstrictor
responses in the rats with experimental early diabetic
nephropathy. However, in the non-diabetic nephropathy
rats of this particular experimental group chloroethylclonidine
did not cause any marked (all P<0.01) shift in these responses
(Figure 4). The overall mean percentage changes in the renal
blood flow of renal failure and non-diabetic nephropathy
and experimental early diabetic nephropathy rats to different
adrenergic stimuli are shown in Table 3.
Discussion
This study, perhaps for the first time, shows the
functional involvement of chloroethylclonidine sensitive
α1B-adrenoceptors in modulating adrenergically-induced renal
vasoconstrictions in renal failure, hypertensive renal failure,
and early diabetic nephropathy rats. In the rats with normal
renal functions, such functional contribution of this
α1-adrenoceptor subtype was absent.
In the rats with renal impairment, the
adrenergically-induced renal vasoconstrictions were either accentuated or
attenuated by chloroethylclonidine, whereas, these responses
in the non-renal failure and non-diabetic nephropathy rats
remain unchanged. A similar set of observations has been
made in several earlier studies on rats with different
pathological states, particularly in some types of experimental
hypertension, heart failure, diabetes, and also in a combined
state of hypertension and
diabetes[10,11,14]. Most importantly, these studies have indicated a possible minor functional
involvement of α1B-adrenoceptors in the
adrenergically-induced renal vasoconstrictions in these rats. In normal rats,
however, no such involvement of α1B-adrenoceptors in
modulating renal vasoconstrictions has been reported. In this
context, the present study investigated whether a similar
phenomenon could exist in some important pathological
conditions characterized with impaired renal functions and
provides further support to the earlier stated view on the
interesting functional characteristics of
α1B-adrenoceptors in renal vasculature.
The present study showed that in the rats with renal
impairment, chloroethylclonidine accentuated the
adrenergically-induced renal vasoconstrictor responses, with some
exceptions in renal failure Wistar Kyoto rats where
chloroethylclonidine attenuated the phenylephrine and
methoxamine induced responses. In general, however, there
was an enhancement of the renal vasoconstrictor responses
elicited by renal nerve stimulation and noradrenaline (renal
failure Wistar Kyoto rats); by renal nerve stimulation,
phenylephrine, and methoxamine (renal failure spontaneously
hypertensive rats), and also by renal nerve stimulation and
all the adrenergic agonists (rats with experimental early
diabetic nephropathy) in the presence of chloroethylclonidine.
It has been shown that in some vasculature,
noradrena-line, which is released due to the stimulation of renal nerves,
caused α1A-adrenoceptor subtype-mediated
vasoconstriction[16,34]. Like endogenously-released noradrenaline,
exogenously administered noradrenaline is also reported to exert
its action through α1A-adrenoceptor subtypes with little or
no evidence for the involvement of α1B-,
α1D-, and even
α2-adrenoceptors[16]. As an apparent difference of some of these
findings, there are reports on the involvement of
α1B- and α1D-adrenoceptors in mediating exogenously administered
and endogenously available noradrenaline in in
vitro experiments[15,16,35]. However, as asserted in some earlier reported
findings, in the presence of chloroethylclonidine and
enhanced sympathetic activity, any such involvement of
α1B- and α1D-adrenoceptors in mediating renal vasoconstriction
will be abolished or impeded. It is stated that
chloroethyl-clonidine has selectivity for
α1-adrenoceptors in the order of
α1B> α1D>>
α1A, and that the α1A-adrenoceptor is insensitive
to chloroethylclonidine, hence, the
α1B- and α1D-adreno-ceptor subtypes will preferentially be inactivated by
chloroethylclonidine[36_40] leaving the
α1A-adrenoceptors to be acted upon by the adrenergic stimuli, leading to
vasoconstrictions. Apart from the possible inactivation by
chloroethylclonidine, the suggested inability of
the α1D-adrenoceptor subtypes to mediate vasoconstrictions in these
pathological states that are characterized with enhanced
sympathetic activity, can further be explained based on the
observation that the α1D-adrenoceptor subtypes are
phosphorylated in the face of enhanced sympathetic
activity[4,13,41]. Indeed, the augmented renal vasoconstrictor response is
reported in several pathophysiological states (spontaneously
hypertensive rats, diabetic hypertensive rats, renal failure
rats, and 2K1C Goldblatt hypertensive rats), as
reported earlier[10,11,14,17].
With this background, it can be suggested that in the
presence of chloroethylclonidine, both renal nerve
stimulation and noradrenaline-induced renal vasoconstrictions was
mediated by α1A-adrenoceptors in the rats with renal
impairment. This view can further be explained based on an
earlier report that in these rats, chloroethylclonidine blocked
α1B-adrenoceptor subtypes and caused
α1A-adrenoceptor subtype-mediated renal vasoconstrictor responses to be
accentuated by the endogenous or exogenously
administered noradrenaline. It can also be suggested that in these
rats there could be an upregulation of
α1A-adrenoceptors or involvement of presynaptic
α1B-adrenoceptors in determining renal vasoconstriction. In the later case, it can be suggested
that when these receptors are blocked by chloroethylclonidine,
the presynaptic autoinhibitory feedback is removed and
allow more noradrenaline to be released, which consequently
resulted in a larger post-synaptic
response[22]. Another possible explanation of these observations in the rats with renal
impairment could be the downregulation of certain
α1-adrenoceptors in the renal vasculature. In support of this
view, it is reported that in diabetes and hypertension, the
α1B-adrenoceptors could be downregulated by the
adrenergic nerves leaving postsynaptic receptors, like the
α1A-adrenoceptor (the predominant type in renal vasculature), to
be enhanced in order to maintain the effectiveness of the
α1-adrenergic nervous
system[32,4].
Chloroethylclonidine showed a similar accentuating
effect on the phenylephrine and methoxamine-mediated
responses in the renal failure spontaneously hypertensive and
experimental early diabetic nephropathy rats, while in the
non-renal failure and non-diabetic nephropathy rats it was
insensitive. These accentuations of renal vasoconstrictions
caused by phenylephrine (selective to the
α1-adrenoceptor subtypes) and methoxamine (selective to the
α1A-and α1D-adrenoceptor subtypes) can be explained in light of our
discussion on the accentuation of noradrenaline and renal nerve
stimulation-mediated responses in the presence of
chloro-ethylclonidine.
In renal failure spontaneously hypertensive rats, it was
further observed a biphasic action of chloroethylclonidine
on the renal nerve stimulation induced changes. It is
reported that there could be a crosstalk relationship between
the α1A- and α1B-adrenoceptor subtypes in terms of
inhibition of α1A-adrenoceptor activities by
α1B-adrenoceptor
subtypes[43]. This phenomenon could help us to explain the
observed biphasic action of chloroethylclonidine in renal
nerve stimulation-induced renal vasoconstrictor responses
in renal failure spontaneously hypertensive rats.
In the case of low dose of chloroethylclonidine, the
puzzling attenuation of the renal nerve-induced
vasoconstrictions in renal failure spontaneously hypertensive rats could
be attributed to the blockade of the unsaturated presynaptic
α1B-adrenoceptors, and it is widely reported that
chloro-ethylclonidine can act presynaptically. In explaining the
accentuation the vasoconstrictor responses in these rats by
a higher dose of chloroethylclonidine, it is possible that the
occupation of the α1B-adrenoceptors leads to an alteration
of the properties of α1A-adrenoceptors so that the normal
agonist and antagonist interaction can not occur. In this
situation, it could be a possibility that the blockade of
α1B-adrenoceptors by chloroethylclonidine would enhance the
sensitivity of the remaining α1-adrenoceptors
(α1A-and α1D-adrenoceptors) so that a potentiation of renal
vasoconstrictor responses occurs. Another possibility is that, in this
particular pathological state with renal failure and hypertension,
there might be an activation of spare receptors due to the
blockade of the α1B-adrenoceptors[17,10,14,44]
.
Together, these data lead us to suggest that in renal failure
Wistar Kyoto and spontaneously hypertensive rats, and also
in the rats with experimental early diabetic nephropathy, there
was a functional involvement of the
α1B-adrenoceptors in modulating adrenergically-induced renal vasoconstric-tions.
The results obtained also lead us to suggest that there might
be a complex interaction between the
chloroethylclonidine sensitive a1-adrenoceptor subtypes. In non-renal failure
and non-diabetic nephropathy rats, the functional
involvement of the α1B-adrenoceptor subtypes was absent.
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