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Introduction
Multiple subtypes of α1-adrenoceptors have been
identified in vascular tissues and are named
α1A-, α1B-, and
α1D-adrenoceptors[1-7]. An RNAse protection assay showed
that the main renal arteries and branches of renal arteries
have mRNA encoding α1A-adrenoceptors in much greater
proportions than those encoding α1B- and
α1D-adrenoceptor subtypes. A functional study demonstrated that
α1A-adrenoceptors primarily mediate the responses to
noradrenaline (NA) in these arteries[8]. However, several earlier
studies reported that adrenergic vasoconstrictions in the
kidneys of normotensive, stroke-prone spontaneously
hypertensive rats, 2-kidney one clip (2K1C), and
deoxycorticosterone acetate (DOCA)-salt hypertensive rats are mediated
by either the α1A-adrenoceptor
subtype[9-11] or by both α1A-
and α1D-adrenoceptor
subtypes[11-15]. Nevertheless, a large
body of experimental evidence has implicated
α1A-adrenoceptors as the major subtype modulating renal
hemodynamics[15].
The kidney is damaged in diabetes as a result of somatic
and autonomic neuropathies as well as vascular
complications[16]. Hypertension and diabetes often occur together,
and the 2 pathological states act synergistically with respect
to cardiovascular damage associated with these disorders.
As hypertension and diabetes frequently occur together,
considerable interest in research has developed on diabetes
and hypertension in relation to the pathophysiology and
sequels of their combined occurrence. Several studies have
reported altered vascular tone in diabetes in terms of
enhanced reactivity of resistance vessels to adrenergic
agonists and alteration in α1-adrenoceptor functionality. In our
previous study, we provided evidence of the involvement of
both post-synaptic α1A- and
α1D-adrenoceptors along with presynaptic
α1B-adrenoceptors in the kidneys of
spontaneously hypertensive rats with
diabetes[17] in mediating adrenergically-induced renal vasoconstrictions. We recently
reported that in another pathological condition, nephrotoxic
renal failure, both post-synaptic (α1A- and
α1D-adrenoceptors) and presynaptic
(α1B-adrenoceptors) were involved in
mediating adrenergically-induced renal vasoconstrictions in rats,
while in non-renal failure rats, only the functional
contribution of post-synaptic α1-adrenoceptors was
observed[5]. A similar disease-dependent change in the functional renal
α1-adrenoceptors has also been reported in rats with
experimental heart failure[18,19]. Collectively, these observations
indicate a pathological state-dependent heterogeneity in the
subtypes of functional α1-adrenoceptor subtypes in the
kidneys of rats. and the presence of disease states have
perhaps played a role in determining the functional subtypes of
the α1-adrenoceptors involved.
With this background, this study set out to evaluate the
functional α1-adrenoceptor subtypes that mediate renal
vasoconstrictor response in diabetic 2K1C Goldblatt
hypertensive rats. The present study is one of a few studies that
focus on the elucidation of functional subtypes of the
α1-adrenoceptor subtypes in a combined state of diabetes and
hypertension, and is the first report on the functional
subtypes of α1-adrenoceptors in a combined state of diabetes
and experimental renovascular hypertension.
Material and methods
Preparation of 2K1C Goldblatt hypertensive rats
The 2K1C Goldblatt hypertensive rats were prepared according
to a method described earlier[10]. Male Sprague_Dawley rats,
approximately 4 weeks old (120 g) were anaesthetized with
pentobarbitone sodium 60 mg/kg intraperitoneally (ip;
Sagatal, Rhone Merieux, Harlow, UK). The dorsal of the
animal was shaved and a retroperitoneal incision was made.
The right kidney was exposed and a piece of wet tissue
paper was placed on the kidney to protect it from damage when
it was retracted to the side using a self-retaining retractor.
The renal artery was dissected, cleared from connective
tissues, and a U-shaped silver clip with a 0.25 mm gap was
slipped around it close to the junction with the aorta. The
free edges of the clip were compressed firmly with Spencer
Wells forceps to prevent it from dislodging. Before suturing
the muscle and skin layers with a number 3 silk thread,
benzylpenicillin G powder was sprinkled around the wounded
area and also on the skin. The animals were allowed to
recover in separate cages for several hours under an anglepoise
lamp. The animals were then placed into single cages for
36_48 h to allow healing and then randomly grouped into groups
of 6. The animals had commercial rat chow with water ad
libitum, and were kept for 5-6 weeks before used in the acute
studies. Only the animals that exhibited a direct mean
arterial blood pressure of 150 mmHg or greater on the day of the
acute experiments were included in the study.
Induction of diabetes Male 2K1C Goldblatt hypertensive
Sprague_Dawley rats (260_310 g) were treated with streptozotocin (55 mg/kg, ip) and caged in groups of 6 for 3
d. During the first 48 h of post-streptozotocin, the rats were
given 5% glucose in drinking water and then plain water ad
libitum. On d 3, the rats were individually placed in the
custom-built, stainless steel metabolic cages. The 24 h water
intake and urine output were measured on d 4 and continued
until d 7. The body weight of the animals was measured on
every alternate day until d 7 on which the acute study was
conducted. Fasting blood glucose was measured by a
commercially-available Peridochrom glucose kit (Boehringer
Manheim, Germany) on the day of the acute experiment. Only
the rats with blood glucose levels of ³200 mg/dL were used
in this study.
Hemodynamic study
General preparation of the animal Eight groups of
animal were used in this study. Groups 1_4 were diabetic
2K1C Goldblatt hypertensive rats, while groups 5_8 were
non-diabetic 2K1C Goldblatt hypertensive rats. The
surgical preparation of the animals for the hemodynamic study
was carried out as reported
earlier[5,6,10]. In brief, the rats were anaesthetized (sodium pentobarbitone 60 mg/kg, ip)
and supplemented with the same anesthetic (12.5
mg·kg_1·h_1) intra-arterially throughout the experiment, given as a
continuous infusion of saline at 6 mL/h. After tracheotomy, the
jugular vein was cannulated for saline infusion, bolus doses
of anesthetic were administered as required, and the carotid
artery was cannulated for blood pressure measurement
using a pressure transducer attached to a computerized data
acquisition system (Powerlab, ADInstrument, Sydney, NSW,
Australia). The kidney was exposed via a midline abdominal
incision. The renal artery was cleared and an
electromagnetic flow probe (EP 100 series, Carolina Medical Instrument,
King, NC, USA) connected to flowmeter (Carolina Medical
Instrument, USA) was placed on the renal artery to allow
direct recording of the renal blood flow with the data
acquisition system. The renal nerves were isolated and carefully
dissected for a short length and placed on fine bipolar
electrodes, which were connected to an electrical stimulator
(Grass S 48 stimulator, Grass Medical Instrument, Quincy,
MA, USA). The iliac artery was cleared and a cannula was
inserted so that its tip lay in the aorta just rostral to the left
renal artery, which allowed for the close intrarenal arterial
administration of saline and drugs.
Experimental protocols The whole experiment was
carried out in 3 distinct phases starting with the
saline-treatment phase. In this phase, saline was infused continuously
and intrarenally, and the renal nerves were stimulated
electrically at increasing frequencies of 1, 2, 4, 6, 8, and 10 Hz and
then in reverse order. In the following experiments, graded
bolus doses of NA (25, 50, 100, and 200 ng), phenylephrine
(PE; 0.25, 0.5, 1, and 2 μg), and methoxamine (ME; 1, 2, 3, and
4 μg) were administered in ascending and then descending
doses. Afterwards, the first dose of antagonist was given,
and 15 min later, the sequence of renal nerve stimulation
(RNS) and the bolus administration of adrenergic agonists
were repeated. For the last phase, the close intrarenal
administration of twice the initial dose of the antagonist was
given, and 15 min later, the nerves were stimulated and the
agonist administration was repeated as carried out in the
previous 2 phases[5,9,10].
The 8 groups of rats, both non-diabetic and diabetic 2K1C
Goldblatt hypertensive Sprague-Dawley rats, were used and
were grouped according to the types of
α1-adrenoceptor subtype-specific antagonists and calcium channel blockers
used in the acute study. These drugs were given in bolus
followed by maintenance doses in the continuous infusion
of saline during the experiment. These drugs along with
their doses used are showed in Table 1.
Drugs Streptozotocin (Sigma, St Louis, MO, USA) was
dissolved in normal saline (0.9% NaCl) and used immediately.
All antagonists and agonists used in this study were
prepared (if required) as stock solutions. 5-Methylurapidil
(Research Biochemicals International, Natick, MA,
USA), a selective antagonist of the α1A-adrenoceptor subtype, was
prepared in 0.04 mol/L lactic acid at a concentration of 100
μg/mL; chloroethylclonidine (Research Biochemicals
International, USA), a selective antagonist of the
α1B-adrenoceptor subtype, was prepared in saline at a
concentration of 100 mg/mL. Nitrendipine (Research Biochemicals
International, USA), an L-type Ca+ channel antagonist, was
prepared in a mixture of PEG-400, glycerol, and distilled water
(969:60:100) at a concentration of 1 mg/mL. Finally, BMY
7378 (Research Biochemicals International, USA), a selective
antagonist of the α1D-adrenoceptor subtype, was prepared at a
concentration of 1 mg/mL in normal saline.
All drugs were kept as frozen aliquots and used within 3
d of their preparation. These stock solutions were diluted in
saline just before being used. The agonists used were NA
(mixed agonist; Levophed, Sanofi Winthrop, London,
England), PE (selective to α1-adrenoceptors; BASF
Pharmaceuticals, Knoll, England, and ME (selective to
α1A-adrenoceptors; (Vasoxine, Calmic Medical
Division,Bristol,England). These drugs were freshly diluted from the frozen
stocks on the day of the experiment.
Data presentation and statistical
analysis The renal vasoconstrictor responses to all the adrenergic stimuli were
taken as an average of 2 values of the decrease of the renal
blood flow for each frequency (RNS) or dose (NA, PE, and
ME) administered in ascending and descending orders. The
basal values of the renal blood flow recorded in each phase
was taken as 100%, and the percentage changes in the
reductions of renal blood flow to each frequency or dose of
adrenergic stimuli in each phase (vehicle and low and high
dose of antagonist-treated phases) were
calculated[5,9,10,17]. Data are presented as mean±SEM and were analyzed by
two-way ANOVA followed by Duncan's post-hoc and multi-range
t-tests (Superanova, Abacus, Berkeley, CA, USA). The
significance was taken at the 5%
level[17].
Results
General observations There was no change
(P>0.05) in the baseline values of renal blood flow among the diabetic
(25.3±2.1
mL·min_1·kg_1) and non-diabetic 2K1C Goldblatt
hypertensive rats (27.6±1.9
mL·min_1·kg_1). However, there
was a change in the mean arterial blood pressure among
these experimental groups. The mean arterial blood
pressure was lower (P<0.05) in the diabetic 2K1C rats compared
to that of the non-diabetic and diabetic 2K1C Goldblatt
hypertensive rats (130.0±5 mmHg vs 143.0±5 mmHg, diabetic
vs non-diabetic 2K1C Goldblatt hypertensive rats) in our
observations. There was a significant difference in the
glycemic status of the diabetic and non-diabetic 2K1C Goldblatt
hypertensive rats (P<0.05). The diabetic 2K1C Goldblatt
hypertensive rats were hyperglycemic, while the non-diabetic
2K1C Goldblatt hypertensive rats had a normal glycemic
status (diabetic 2K1C Goldblatt hypertensive rats 298.0±11.6
mg/dL vs non-diabetic 2K1C Goldblatt hypertensive rats
138.2± 8.5 mg/dL).
Renal vasoconstrictor responses
RNS RNS produced frequency-dependent renal
vasoconstrictions in both the non-diabetic and diabetic 2K1C
Goldblatt hypertensive rats (all P<0.05). Nitrendipine and
5-methylurapidil significantly attenuated the RNS-induced
renal vasoconstrictions in the non-diabetic and diabetic 2K1C
rats (P<0.05). BMY 7378 also attenuated these
responses, but only in the non-diabetic 2K1C rats
(P<0.05), while in the diabetic 2K1C rats, it accentuated these responses
(P<0.05). Chloroethylclonidine accentuated these responses in both
the diabetic and non-diabetic 2K1C Goldblatt hypertensive
rats (all P<0.05; Figure 1; Table 2).
NA NA-induced renal vasoconstrictor responses were
dose dependent in both experimental groups
(P<0.05). In the diabetic and non-diabetic 2K1C Goldblatt hypertensive
rats, nitrendipine and 5-methylurapidil significantly
attenuated the NA-induced renal vasoconstrictor responses
(all P<0.05). Interestingly, chloroethylclonidine significantly
accentuated these responses in the diabetic and non-diabetic
2K1C Goldblatt hypertensive rats (P<0.05). BMY 7378 it was
also of interest as it caused significant attenuation of the
NA-induced renal vasoconstrictor responses in the
non-diabetic 2K1C Goldblatt hypertensive rats
(P<0.05), while in the diabetic 2K1C Goldblatt hypertensive rats, BMY 7378
accentuated these responses (P<0.05; Table 2; Figure 2).
PE PE produced dose-dependent vasoconstrictor
responses in both diabetic and non-diabetic 2K1C rats (all
P<0.05). Nitrendipine and 5-methylurapidil attenuated the PE-induced
renal vasoconstrictor responses in both the non-diabetic
and diabetic 2K1C Goldblatt hypertensive rats
(P<0.05). BMY 7378 also caused similar attenuating effects of the
PE-induced renal vasoconstrictor responses; however, only in
the non-diabetic 2K1C Goldblatt hypertensive rats
(all P<0.05). In the diabetic 2K1C Goldblatt hypertensive rats, BMY
7378 significantly accentuated the PE-induced renal
vasoconstrictor responses (P<0.05). In both the diabetic and
non-diabetic 2K1C Goldblatt hypertensive rats, chloroethylclonidine significantly accentuated the
PE-induced renal vasoconstrictor responses (all
P<0.05; Table 2; Figure 3).
ME Like other adrenergic stimuli, ME also produced
dose-dependent changes in the renal blood flow of the
non-diabetic and diabetic 2K1C rats (all P<0.05). In both the
diabetic and non-diabetic 2K1C Goldblatt hypertensive rats,
nitrendipine and 5-methylurapidil significantly attenuated the
ME-induced renal vasoconstrictor responses (all
P<0.05). A similar significant attenuation of the ME-induced renal
vasoconstrictor responses was also caused by BMY 7378, but
only in the non-diabetic 2K1C Goldblatt hypertensive rats
(P<0.05). Significant accentuation of the ME-induced
changes occurred in the diabetic 2K1C Goldblatt
hypertensive rats (P<0.05), while in the non-diabetic 2K1C Goldblatt
hypertensive rats, it significantly attenuated these responses
(all P<0.05). Chloroethylclonidine significantly accentuated
the ME-induced renal vasoconstrictor responses in both the
diabetic and non-diabetic 2K1C Goldblatt hypertensive rats
(all P<0.05; Table 2; Figure 4).
Discussion
Renal vasculature is richly innervated by adrenergic
nerves in which α1A-adrenoceptors have consistently been
recognized as the predominate subtype over the other two
α1-adrenoceptor subtypes in terms of density and
functionality[20]. In relation to this observation,
adrenergically-induced renal vasoconstriction in normotensive rats,
stroke-prone spontaneously hypertensive rats, DOCA-salt, and
2K1C Goldblatt hypertensive rats are found to be mediated
by α1A-adrenoceptors[9,10,21_25]
. Further studies have, however, described that the renal vasoconstrictor responses are
mediated by both α1A-[11] and/or
α1D-adrenoceptors[11,12,26,27]
. There are reports on the functional co-existence of
α1A- and α1D-adrenoceptor subtypes in the renal vasculature of rats
with normal[15] and pathophysiological states like in diabetes,
hypertensive diabetes, heart failure, and renal
failure[5,17_19].
As discussed above, although there are number of
research that have reported the functional subtypes of
α1-adrenoceptor subtypes in the renal vasculature, there is still
a large paucity of information on this issue. This is
particularly true for the functional involvement of
α1-adrenoceptor subtypes in the renal vasculature of rats with pathological
states[5,17-19]. It has been reported that some
pathophysiological states may change the composition of the
α1-adrenoceptors present in different
vasculatures[18]. With this background, a hypothesis is formulated that in certain
pathological conditions there would be a shift in the functional
α1-adrenoceptor subtypes mediating adrenergically-induced
renal vasoconstriction. In relation to this, we previously
reported that there was a shift in the functional contribution
of α1-adrenoceptor subtypes in the renal vasculature of rats
with certain disease states like diabetes, a combined state of
genetic hypertension and diabetes, heart failure, and a
combined state of heart failure and
hypertension[17-19]. In the present study, we focused on a unique pathological state
that is characterized with diabetes and experimental
renovascular hypertension (2K1C Goldblatt hypertension).
The results obtained in this study showed that in some
cases, the renal vasoconstrictor responses caused by the
neural and adrenergic stimuli were significantly lower in the
diabetic 2K1C rats compared to that of the non-diabetic 2K1C
Goldblatt hypertensive rats. These observations led us to
suggest that in the diabetic 2K1C Goldblatt hypertensive
rats, the sympathetic nervous system activity was perhaps
enhanced. Such enhancement of the sympathetic nervous
system in these rats might have caused a reduction in the
sensitivity of the adrenoceptors and/or a potential
downregulation of these receptors in order to compromise
the impact of higher vascular sympathetic tone on the
vasculature. Interestingly, in some cases, it has been further
observed that the renal vasoconstrictions are markedly higher
in diabetic 2K1C Goldblatt hypertensive rats. This could be
due to a possible autonomic dysfunction in these rats, as
degenerative changes are observed in the
streptozotocin-induced diabetic rats from 3 d of the streptozotocin treatment.
The autonomic dysfunction in the diabetic 2K1C Goldblatt
hypertensive rats was indicated by their markedly lower blood
pressure[28_30].
In the present study, we found that in the non-diabetic
2K1C rats, the adrenergically-induced renal vasoconstrictor
responses were attenuated by all the antagonists except
chloroethylclonidine. These observations strongly
suggested the functional contribution of
α1A- and α1D-adrenoceptor subtypes in mediating the
adrenergically-induced renal vasoconstrictions in these rats. These
observations are supported by several earlier studies reporting the
functional involvement of multiple subtypes of
α1-adrenoceptors (α1A- and
α1D-adrenoceptor subtypes) in the renal vasculature of rats with either normal physiological
state or with certain pathophysiological
states[5,12,15,17]. Unlike the non-diabetic 2K1C Goldblatt hypertensive rats, in
the diabetic 2K1C Goldblatt hypertensive rats, the
adrenergically-induced renal vascular responses were attenuated
by nitrendipine and 5-methylurapidil, hence, indicating a
strong functional contribution of α1A-adrenoceptor subtypes.
It is also observed that in these rats, these adrenergic
responses were either enhanced or remained unaltered by
chloroethylclonidine and BMY 7378. These observations
further strengthen the view that in the diabetic 2K1C Goldblatt
hypertensive rats, the α1A-adrenoceptor subtypes were to a
large extent involved in mediating the adrenergically-induced
renal vasoconstriction and that the functional involvement
of α1D-adrenoceptor subtypes was minimal. These
observations are indeed unique considering the pathological state
of the rats (diabetic 2K1C Goldblatt hypertensive rats), and
support an earlier view that it is α1A-adrenoceptor subtypes
that primarily regulate the renal
hemodynamics[5,15,17]. The present study also demonstrated some interesting
observations in which chloroethylclonidine caused the
accentuation of the adrenergically-induced renal vasoconstrictor
responses in both diabetic and non-diabetic 2K1C Goldblatt
hypertensive rats. Similar observations have been made in
several earlier studies in rats with diabetes, hypertensive
diabetes, and in cisplatin-induced renal
failure[5,17].
Chloroethylclonidine is found to cause the accentuation
of RNS (both in diabetic and non-diabetic 2K1C Goldblatt
hypertensive rats) and NA (both diabetic and non-diabetic
2K1C Goldblatt hypertensive rats)-induced renal
vasoconstrictor responses in the experimental animal groups used in
this study. These observations can be explained in light of
the findings that in some vasculatures, the NA, which is
released due to the stimulation of renal nerve, caused
α1A-adrenoceptor subtype-mediated
vasoconstriction[31,32]. Moreover, like endogenously-released NA,
exogenously-administered NA has also been reported to exert its action
through α1A-adrenoceptor subtypes with little or no evidence
for the involvement of α1B-,
α1D-, and even
a2-adrenoceptors[32]. However, as asserted in some earlier 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[33-35]. It has been stated that chloroethylclonidine has
selectivity for α1-adrenoceptors in the order of
α1B>α1D>>α1A
, and the α1A-adrenoceptor is insensitive to
chloroethylclonidine. Hence, it can be suggested that
α1B- and α1D-adrenoceptor subtypes will be preferentially inactivated by
chloroethyl-clonidine[33-36] leaving
α1A-adrenoceptors to be acted upon by the adrenergic stimuli leading to vasoconstrictions.
With this background, it can be suggested that chloroethylclonidine blocks
α1B-adrenoceptor subtypes and causes
α1A-adrenoceptor subtype-mediated renal
vasoconstrictor responses to be accentuated by the endogenous or
exogenously-administered NA. 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
auto-inhibitory feedback is removed and allows more NA to be
released, which consequently results in a larger
post-synaptic response[37]. Another possible explanation of these
observations could be the downregulation of certain
α1-adrenoceptors in the renal vasculature. In support of this
view, it was reported that in diabetes and hypertension, the
α1B-adrenoceptors could be downregulated by the
adrenergic nerve leaving post-synaptic receptors like the
α1A-adrenoceptor (the predominant type in the renal vasculature)
to be enhanced in order to maintain the effectiveness of the
α1-adrenergic nervous
system[38]. In the diabetic and non-diabetic 2K1C rats, chloroethylclonidine showed a similar
accentuating effect on the vasoconstrictions caused by PE
and ME-mediated responses. These accentuations of the
renal vasoconstriction caused by PE (selective to
α1-adrenoceptor subtypes) and ME (selective to
α1A-adrenoceptor subtypes) can be explained in light of our
discussion on the accentuation of NA and RNS-mediated
responses in the presence of chloroethylclonidine. This study
also reported that in the diabetic 2K1C rats, the
α1D-adrenoceptor subtype selective antagonist BMY 7378 caused
the accentuation of some of the adrenergically (NA, PE, and
ME)-induced renal vasoconstrictor responses. This
observation could be explained based on the notion that this
compound also has low-affinity, presynaptic
α1B-adrenoceptors, hence, enhancing the effect of the post-synaptic
α1-adrenoceptor like the
α1A-subtypes[38-40].
The present study has clearly shown a difference in the
functional population of α1-adrenoceptor subtypes in the
renal vasculature of 2K1C Goldblatt hypertensive rats with
and without diabetes. In non-diabetic 2K1C rats, the
adrenergically-induced renal vasoconstrictor responses were
largely mediated by multiple subtypes of
α1-adrenoceptors (α1A- and
α1D-adrenoceptors), while in the diabetic 2K1C rats,
these responses were largely mediated by a single subtype
(α1A-adrenoceptor subtype). A minor involvement of
presynaptic α1-adrenoceptors along with a complex interaction
between some of the subtypes of α1-adrenoceptors (particularly
between the α1A- and α1B-subtypes) was also apparent in the
rats of either experimental group. Although some of these
observations in terms of the functional involvement of
α1-adrenoceptors in the renal vasculature are already stated in
several earlier studies, the data pertaining to diabetic and
non-diabetic 2K1C Goldblatt hypertensive rats are unique.
References
1 Hieble JP, Bylund DB, Clark DE, Eikenburg DC, Langer SZ,
Lefkowitz RJ, et al. International Union of Pharmacology X.
Recommendation for nomenclature of α1-adrenoceptors:
consensus update. Pharmacol Rev 1995; 47: 267_70.
2 Bylund DB, Regan JW, Faber JE, Hieble JP, Triggle CR, Rufollo
RR. Vascular a-adrenoceptors: from the gene to the human. Can
J Physiol Pharmacol 1995; 73: 533_43.
3 Vargas HM, Gorman AJ. Vascular
α1- adrenergic receptor subtypes in the regulation of arterial pressure. Life Sci 1995; 57:
2291_308.
4 Bishop MJ. Recent advances in the discovery of
α1-adrenoceptor agonists. Curr Top Med Chem 2007; 7: 135_45.
5 Khan AH, Sattar MA, Abdullah NA, Johns EJ. Influence of
cisplatin-induced renal failure on the alpha (1)-adrenoceptor
subtype causing vasoconstriction in the kidney of the rat. Eur J
Pharmacol 2007; 569: 110_8.
6 Hye Khan MA, Sattar MA, Abdullah NA, Johns EJ. Cisplatin
cause altered renal hemodynamics in rats: role of augmented
a-adrenergic responsiveness. Exp Toxicol Pathol 2007; 53:
253_60.
7 Rosini M, Bolognesi ML, Giarrdina D, Minarini A, Tumitatti V,
Melchiorre C. Recent advances in α1-adrenoceptor antagonists
as pharmacological tools and therapeutic agents. Curr Top Med
Chem 2007; 7: 147_62.
8 Moriyama N, Kurooka Y, Nasu K, Akiyama K, Takeuchi T,
Nishimatsu H, et al. Distribution of
α1-adrenoceptor subtype mRNA and identification of subtype responsible for renovascular
contraction in human renal artery. Life Sci 2000; 66: 915_26.
9 Abdul Sattar M, Johns EJ. Alpha 1-adrenoceptor subtypes
mediating adrenergic vasoconstriction in kidney, one-clip Goldblatt
and deoxycorticosterone acetate-salt hypertensive rats. J
Cardiovasc Pharmacol 1994; 24: 420_8.
10 Sattar MA, Johns EJ. Evidence for an
α1-adrenoceptor subtype mediating adrenergic vasoconstriction in Wistar normotensive
and SPSHR kidney. J Cardiovasc Pharmacol 1994; 23: 232_9.
11 Villalobos-Molina R, Ibarra M.
α1-adrenoceptor mediating contraction in arteries of normotensive and SH rats are of
α1D- or α1A-subtypes. Eur J Pharmacol 1996; 298: 257_63.
12 Villalobos-Molina R, Lopez-Guerrero JJ, Ibarra M.
α1D- and α1A-adrenoceptors mediate contraction in rat renal artery. Eur J
Pharmacol 1997; 322: 225_7.
13 Eltze M, Konig H, Ullrich B, Grebe T. Buspirone functionally
discriminates tissues endowed with α1-adrenoceptor subtypes A,
B, D and L. Eur J Pharmacol 1999; 378: 69_83.
14 Satoh M, Enomoto K, Takayanagi I, Koike K. Analysis of
α1-adrenoceptor subtypes in rabbit aorta and arteries: regional
difference and co-existence. Eur J Pharmacol 1999; 374: 229_40.
15 Salomonsson M, Brannstrom K, Arendshorst WJ. Alpha
(1)-adrenoceptor subtypes in rat renal resistance vessels:
in vivo and in vitro studies. Am J Physiol 2000; 278: F138_47.
16 Porte D, Schwartz MW. Diabetes complications. Why is
glucose potentially toxic? Science 1996; 272: 699_700.
17 Armenia A, Munavvar AS, Abdullah NA, Helmi A, Johns EJ. The
contribution of adrenoceptor subtypes in the renal vasculature of
diabetic spontaneously hypertensive rats. Br J Pharmacol 2004;
142: 719_26.
18 Abbas SA, Munavvar AS, Abdullah NA, Johns EJ. Involvement
of α1-adrenoceptor subtypes in the cardiac failure in
spontaneously hypertensive rats. J Basic Appl Sci 2006; 2: 59_69.
19 Abbas SA, Munavvar AS, Abdullah NA, Johns EJ. Role of
alpha1-adrenoceptor subtypes in renal haemodynamics in heart failure
and diabetic SD rats. Can J Pure Appl Sci 2007; 1: 21_34.
20 Stassen FR, Maas R, Schiffers, PMH, Janssen GM, De Mey JG. A
positive and Reversible relationship between adrenergic nerves
and alpha1A-adrenoceptors in rat arteries. J Pharmacol Exp
Ther 1998; 284: 399_405.
21 Elhawary AM, Pettinger WA, Wolff DW. Subtype-selective
a1-adrenoceptor alkylation in the rat kidney and its effect on the
vascular pressor response. J Pharmacol Exp Ther 1992; 260:
709_13.
22 Villalobos-Molina R, Lopez-Guerrero JJ, Ibarra M. Functional
evidence of a1D -adrenoceptors in vasculature of young and adults
spontaneously hypertensive rats. Br J Pharmacol 1999;126:
1534_6.
23 Blue DR, Vimont RL, Clarke DE. Evidence for a noradrenergic
innervation to α1A-adrenoceptors in rat kidney. Br J Pharmacol
1992; 107: 414_7.
24 Blue DR, Bonchaus DW, Ford APDW, Pfister JR, Syarif NA,
Shieh IA, et al. Functional evidence equating the
pharmacologically-defined a1A- and cloned
α1C-adrenoceptor: studies in isolated perfused kidney of rat. Br J Pharmacol 1995; 115: 283_94.
25 Perez DM, Piascik MT, Malik N, Gaivin R, Graham RM. Cloning,
expression, and tissue distribution of the rat homolog of the
bovine α1C-adrenergic receptor provide evidence for its
classification as the α1A-subtype. Pharmacology 1994; 46: 823_31.
26 Zhu W, Zhang Y, Han C. Characterization of subtype
α1-adrenoceptor mediating vasoconstriction in perfused rat hind
limb. Eur J Pharmacol 1997; 329: 55_61.
27 Hrometz SL, Edelmann SE, McCune DF, Olges JR, Hadley RW,
Perez DM, et al. Expression of multiple
α1-adrenoceptors on vascular smooth muscle: correlation with the regulation of
contraction. J Pharmacol Exp Ther 1999; 290: 452_63.
28 Maeda CY, Fernandes TG, Timm HB, Irigoyen MC. Autonomic
dysfunction in short-term experimental diabetes. Hypertension
1995; 26: 1100_4.
29 Schaan BD, Dall'Ago P, Maeda CY, Ferlin E, Fernandes TG,
Schmid H, et al. Relationship between cardiovascular
dysfunction and hyperglycemia in streptozotocin-induced diabetes in
rats. Braz J Med Biol Res 2004; 37: 1895_902.
30 Maeda CY, Fernandes TG, Lulhier F, Irigoyen MC.
Streptozotocin diabetes modifies arterial pressure and baroreflex
sensitivity in rats. Braz J Med Biol Res 1995; 28: 497_501.
31 Jarajapu YPR, Hillier C, MacDonald A. The
α1A-adrenoceptor subtypes mediate contraction in rat femoral resistance arteries.
Eur J Pharmacol 2000; 422: 127_35.
32 Zacharia J, Hillar C, MacDonald A.
α1-adrenoceptor subtypes involved in vasoconstrictor responses to exogenous and neurally
released in rat femoral resistance arteries. Br J Pharmacol 2004;
141: 915_24.
33 Hirasawa A, Sugawara T, Awaji T, Tsumaya K, Ito H, Tsujimoto
G. Subtype-species differences in sub-cellular localization of
α1-adrenoceptors: chloroethylclonidine
preferentially alkylates the accessible cell surface
α1-adrenoceptors irrespective of the subtype. Mol Pharmacol 1997; 52: 764_70.
34 Yang M, Reese J, Cotecchia S, Michel MC. Murine
alpha1-adrenoceptor subtypes. I. Radioligand binding studies. J
Pharmacol Exp Ther 1998; 286: 841_7.
35 Gómez-Zamudio J, Lázaro-Suárez ML, Villalobos-Molina R,
Urquiza-Marín H. Evidence for the use of agonists to
characterize α1- adrenoceptors in isolated arteries of the rat. Proc West
Pharmacol Soc 2002; 45: 159_60.
36 Arévalo-León LE, Gallardo-Ortíz IA, Urquiza-Marín H,
Villalobos-Molina R. Evidence for the role of
alphα1D- and α1A-adrenoceptors
in contraction of rat mesenteric artery. Vascul Pharmacol 2003;
40: 9196.
37 Li Z, Silver WP, Koman LA, Strandhoy JW, Rosencrance E,
Gordon S, et al. Role of
a1A-adrenoceptor subtypes mediating constriction of the rabbit ear thermoregulatory microvasculature.
J Orthop Res 2000; 18: 156_63.
38 Stassen FR, Willemsen MJ, Janssen GM, De Mey JG. Alpha
1-adrenoceptor subtypes in rat aorta and mesenteric small arteries
are preserved during left ventricular dysfunction
post-myocardial infarction. Cardiovasc Res 1997; 33: 706_13.
39 Goetz AS, King HK, Ward SD, True TA, Rimele TJ, Saussy DL.
BMY 7378 is a selective antagonist of the D subtype of
α1-adrenoceptors. Eur J Pharmacol 1995; 272: R5_R6.
40 Zhou L, Varga S. Vascular
α1D-adrenoceptors have a role in the pressor response to phenylephrine in pithed rat. Eur J Pharmacol
1996; 305: 173_6.
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