ORIGINAL ARTICLE
Role of protein kinase C in Ca channel blocker-induced
renal arteriolar dilation in spontaneously hypertensive rats
– Studies in the isolated perfused hydronephrotic kidney –Koichi Hayashi, Shu Wakino, Yuri Ozawa, Koichiro Homma, Takeshi Kanda, Ken Okubo, Ichiro Takamatsu,
Satoru Tatematsu, Hiroo Kumagai and Takao Saruta
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan(Received for publication on December 14, 2004)(Revised for publication on January 7, 2005)(Accepted for publication on February 17, 2005)

Abstract. The present study examined the role of L-/T-type Ca channels and the interaction between
these channels and protein kinase C (PKC) in hypertension. The isolated perfused hydronephrotic rat
kidney model was used to visualize directly the renal microvascular effects of L-/T-type Ca channel
blockers (nifedipine and mibefradil, respectively). Nifedipine reversed the angiotensin II-induced constriction of afferent, but not efferent, arterioles in kidneys from Wistar-Kyoto rats (WKY), and similar
magnitude in dilation was observed in spontaneously hypertensive rats (SHR). Although mibefradil
elicited dilation of both arterioles, the afferent arteriolar dilation was less in SHR than in WKY(57 G 5% vs. 80 G 4% reversal at 1 mmol/L). The pretreatment with staurosporine did not alter theangiotensin II-induced afferent arteriolar constriction in WKY, but attenuated this response in SHR.
Furthermore, staurosporine enhanced the nifedipine-induced afferent arteriolar dilation (62 G 3% vs.
50 G 3% reversal at 10 nmol/L), and restored the attenuated afferent arteriolar response to mibefradilin SHR. The pretreatment with thapsigargin (a blocker of IP3-mediated intracellular calcium release)prevented the angiotensin II-induced afferent arteriolar constriction in WKY, but caused a signiﬁcantconstriction of afferent arterioles in SHR and efferent arterioles in WKY and SHR; in this setting,mibefradil did not alter efferent arteriolar tone. In conclusion, although both L-type (nifedipine) andT-type Ca channel blockers (mibefradil) exerted potent vasodilation of rat renal microvessels, theseactions were modiﬁed by PKC, which determined the afferent arteriolar sensitivity to these blockers
in SHR. Furthermore, the enhancement in nifedipine-induced afferent arteriolar dilation by staurosporine in SHR suggests that L-type Ca channel activity is augmented in hypertensive animals. (Keio J
Med 54 (2): 102–108, June 2005)
Key words: hypertension, protein kinase C, mibefradil, afferent arterioles, efferent arterioles

Introduction
It has been proposed that multiple mechanisms are
responsible for the augmented vascular tone in hypertension. In previous studies, protein kinase C (PKC) is
demonstrated to be augmented in vascular smooth muscle cells from spontaneously hypertensive rats (SHR),
compared with that in normotensive littermates.1,2 Furthermore, the activity of voltage-dependent Ca channels
is altered in hypertensive animals.3 Among the voltagedependent Ca channels, the role of L-type Ca channels

has been extensively investigated, and has been reported to be enhanced in hypertensive animals.3,4Recently, a growing body of evidence has accrued thatT-type Ca channels plays an important role in the cardiovascular system, and is rendered teleologically activein the tissues where the electrical function is periodically ﬂuctuated, including cardiac pacemaker cells.5
Furthermore, several lines of studies have demonstrated that the blockade of T-type Ca channels causes
sustained vasodilation of renal arterioles6,7 and mesenteric arteries.8 Despite widespread distribution of

Reprint requests to: Dr. Koichi Hayashi, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjukuku, Tokyo 160-8582, Japan, e-mail: khayashi@sc.itc.keio.ac.jp102Keio J Med 2005; 54 (2): 102–108

T-type Ca channels in the vascular tissue, the role ofthese Ca channels remains undetermined in hypertensive animals.
The renal vasculature possesses unique characteristics with regard to the distinct microvascular property
of afferent and efferent arterioles. Previous studies
revealed that vascular smooth muscle cells of afferent
arterioles manifest spindle-shaped morphology andcontain both SM1 and SM2 myosine heavy chain isoforms, whereas those of efferent arterioles exhibit starlike shape and possess only a SM1 isoform.9,10 Consistently, L-type Ca channels are distributed at theafferent, but not efferent, arteriole.11–13 In contrast,
T-type Ca channels are present in both afferent andefferent arterioles, and actually contribute substantiallyto the regulation of renal microvascular tone.6,7 Additionally, several lines of studies have clariﬁed differing
mechanisms for intracellular signal transduction in afferent and efferent arterioles.14,15 In the afferent arteriole, inositol 1,4,5-trisphosphate (IP3) stimulates sarcoplasmic reticulum, and elicits the intracellular Ca
release, which ﬁnally gates L-type Ca channels.14,15 In
contrast, in the efferent arteriole, both IP3 and diacylglycerol participate in the efferent arteriolar constrictor mechanism.14,15 The IP3-mediated stimulationof sarcoplasmic reticulum is suggested to induce the
Ca entry, possibly through store-operated Ca channels.14,16,17 Furthermore, diacylglycerol and PKC arereported to activate transient receptor potential (TRP)
channels18 or nonselective cation channels,19 which
subsequently accelerate the Ca entry from the extracellular space. Of note, both mibefradil20 and nickel,
relatively selective inhibitors for T-type Ca channels,
potently dilate efferent arterioles, thus suggesting thatT-type Ca channels participate in the vasomotor mechanisms of the efferent arteriole, including IP3- and
PKC-associated pathways. Although the divergent responsiveness of afferent and efferent arterioles controls
glomerular capillary pressure, the alteration in the vascular tone of these arterioles in hypertension is not fully
elucidated.
In the present study, we examined the effect of Ltype and T-type Ca channel blockers on angiotensin(ANG) II-induced constriction of afferent and efferent
arterioles in hypertensive animals, and compared therole of L- and T-type Ca channels in mediating the renal microvascular tone in the normotensive control.
Methods
Six-week-old male Wistar-Kyoto rats (WKY; n ¼ 18)
and spontaneously hypertensive rats (SHR; n ¼ 18)
were used for renal perfusion study. Under ether anesthesia, chronic hydronephrosis was established by ligation of the right ureter through a small mid-abdominal

103

incision;6,14,21 this model facilitates direct visualizationof the renal microcirculation, with qualitatively parallel responses of renal microvessels with those expectedfrom renal hemodynamic responses in normal kidneys.22,23 Furthermore, lack of tubuloglomerular feedback24 or systemic inﬂuence of neural and hormonal
factors would allow direct assessment of renal microvascular responses. After 8–10 weeks, at which time
renal tubular atrophy had progressed to a stage thatallowed direct microscopic visualization of renal microvessels, the kidneys were harvested for perfusion study.
All procedures involving this study were conductedfollowing the guidelines of the Animal Care Committeeof Keio University. The animals had free access towater and chows throughout the study.
The rats were anesthetized with ether, and the abdominal cavity was exposed by midline incision. The
renal artery of the hydronephrotic kidney was cannulated in situ through the superior mesenteric artery
across the aorta. The hydronephrotic kidney was placedon the stage of an inverted microscope (IMT-2, Olympus, Tokyo, Japan) modiﬁed to accommodate a heatedchamber equipped with a thin glass viewing port on thebottom surface. Kidneys were allowed to equilibrate for
30 min before initiating experimental procedures.
Kidneys were perfused with medium consisting of a
Krebs-Ringer bicarbonate buffer containing 5 mmol/L
D-glucose, 7.5% bovine serum albumin (Sigma, St.
Louis, MO), and a complement of amino acids.25 The
perfusion apparatus is illustrated in our previous publication.22 The perfusion medium was saturated with agas mixture of 95%O2 /5%CO2 within a pressurized
reservoir. The perfusion pressure, monitored at thelevel of the renal artery, was maintained constant at
80 mmHg by adjusting the back-pressure-type regulator (Model 10BP, Fairchild Industrial products Co.,
Winston-Salem, NC).
Vessel diameters were measured as detailed previously.21,22 In brief, video images from a video camera(model XC-77, Sony, Tokyo) were recorded with avideocassette recorder and transmitted to a computer(PS55/Model 5551, IBM Japan, Tokyo) equipped with avideo acquisition board (Targa 16þ, Truevision Inc.,
Indianapolis, IN). Segments of afferent and efferent
arterioles approximately 50 mm in length, near the glomerulus, were evaluated at 0.5–1.0 second intervals.
Mean vessel diameter was determined by averaging
all measurements obtained during the plateau of the
response.
Experimental protocols
1) Effect of nifedipine and mibefradil on ANG IIinduced renal vasoconstriction
Following the observation of ANG II (0.3 nmol/L)-

104

Hayashi K, et al: Ca channels and PKC in hypertension

induced vasoconstrictor responses, the vasodilator effect of nifedipine (0.01, 0.1, and 1 mmol/L) and mibefradil (0.01, 0.1, and 1 mmol/L) was assessed in kidneys
from both WKY and SHR. Thereafter, losartan (10mmol/L) was added directly into the perfusate toeliminate the remaining vasoconstrictor tone of thesearterioles.

Table 1 Effects of Angiotensin II on Renal Afferent and Efferent
Arteriolar Diameters
Diameter (mm)WKY2) Effects of staurosporine on nifedipine/mibefradilinduced changes in renal microvascular tone
The ANG II-induced vasoconstriction of renal arterioles involves both PKC- and IP3-mediated pathways
as intracellular signaling mechanisms.14,15 Initially, 50
nmol/L staurosporine was administered into the perfusate. Following the induction of ANG II (0.3 nmol/L)induced renal vasoconstriction, nifedipine (0.01, 0.1 and1 mmol/L) or mibefradil (0.01, 0.1 and 1 mmol/L) was
added to the perfusate, and the vasodilator effect ofthese agents was evaluated in WKY and SHR.

SHR

Afferent arterioles (n ¼ 12)
Efferent arterioles (n ¼ 12)
Afferent arterioles (n ¼ 12)
Efferent Arterioles (n ¼ 12)

Baseline

Angiotensin II(0.3 nmol/L)

14.6 G 0.3
13.0 G 0.3
14.2 G 0.2
12.8 G 0.3

10.1 G 0.3*
9.0 G 0.4*
9.0 G 0.3*
9.1 G 0.3*

WKY; Wistar-Kyoto rats, SHR; spontaneously hypertensive rats.
*, p < 0.01 vs. Baseline.

3) Effects of thapsigargin on nifedipine/mibefradilinduced changes in renal microvascular tone
The effect of nifedipine and mibefradil on the ANG
II-induced constriction of renal arterioles was evaluatedduring the inhibition of the IP3 pathway by thapsigargin. In the presence of thapsigargin (1 mmol/L),
which depleted sarcoplasmic Ca store by inhibiting
sarcoplasmic Ca-ATPase26 and thus mainly blocked
the IP3-mediated vascular tone, ANG II (0.3 nmol/L)
was added to establish the basal vascular tone. Subsequently, the effect of nifedipine (0.01, 0.1 and 1 mmol/L) or mibefradil (0.01, 0.1 and 1 mmol/L) on the ANG
II-induced renal vascular tone was evaluated in WKY
and SHR.
Analysis of data
Data are expressed as the means G SEM. Data wereanalyzed by 2-way ANOVA followed by Bonferroni’s
post hoc test. P values < 0.05 were considered statistically signiﬁcant.

Fig. 1 Effects of nifedipine and mibefradil on angiotensin II-induced
constriction of renal arterioles in kidneys from WKY and SHR. Nifedipine caused similar dilation of afferent arterioles in WKY and SHR,
whereas mibefradil-induced dilation of the afferent arteriole wasattenuated in SHR. Efferent arterioles did not respond to nifedipine,or exhibited nearly identical dilator response to mibefradil in WKY
and SHR. Results are means G SEM. y, p < 0.05 vs. WKY.

Results
Comparison of nifedipine- and mibefradil-induced renal
vasodilation in WKY and SHR
Renal arteriolar responses to nifedipine and mibefradil in kidneys from SHR were evaluated, and werecompared with those in WKY kidneys (Table 1). In
WKY, ANG II (0.3 nmol/L) elicited marked vasoconstriction of afferent (30 G 3% decrement in diameter, n ¼ 12) and efferent arterioles (31 G 4% decrement
in diameter, n ¼ 12). In SHR kidneys, afferent arteriolar vasoconstrictor responses to ANG II (36 G 3% dec-

rement in diameter, n ¼ 12) tended to be greater thanthose in WKY (p ¼ 0.1). Efferent arteriolar responses(29 G 5% decrement in diameter, n ¼ 12) did not differ
from those from WKY kidneys (p > 0.5).
Nifedipine caused a dose-dependent vasodilation of
the ANG II-constricted afferent arteriole, with nearly
identical responses observed in WKY (n ¼ 6) and SHR(n ¼ 6; Fig. 1, upper). Nifedipine however failed to relax the efferent arteriolar constriction in either WKY or
SHR. Mibefradil also inhibited the afferent arteriolar
responses to ANG II in a dose-dependent manner(n ¼ 6; Fig. 1, lower left). Of note, the vasodilator

Keio J Med 2005; 54 (2): 102–108

105

Fig. 2 Role of protein kinase C and intracellular Ca release inangiotensin II-induced constriction of renal arterioles from WKY andSHR kidneys. In WKY, angiotensin (ANG, 0.3 nmol/L) II-induced
constriction of afferent arterioles was unaffected by the pretreatment
with staurosporine (50 nmol/L, ﬁlled bars), but completely abolishedby thapsigargin (1 mmol/L, hatched bars). In SHR kidneys, however,staurosporine blunted the constrictor responses to ANG II of bothafferent and efferent arterioles. Results are means G SEM. *, p < 0.05
vs. ANG II (open bars); **, p < 0.01 vs. ANG II.

action of mibefradil on the afferent arteriole wasblunted in SHR, compared with that in WKY (100nmol/L, 30 G 3% vs. 48 G 4%, p < 0.05; 1 mmol/L,
57 G 5% vs. 80 G 4%, p < 0.05; n ¼ 6). In contrast, efferent arterioles manifested similar responsiveness tomibefradil in WKY (n ¼ 6) and SHR kidneys (n ¼ 6).

Fig. 3 Effect of nifedipine and mibefradil on angiotensin II-induced
constriction of renal arterioles in the presence of staurosporine. In
afferent arterioles from SHR kidneys, the pretreatment with staurosporine (50 nmol/L) enhanced the vasodilator responses to nifedipine(upper), and restored the blunted responsiveness to mibefradil, but
had no effect on efferent arteriolar responses to mibefradil (lower).
Results are means G SEM. y, p < 0.05 vs. WKY.

Effects of staurosporine/thapsigargin on nifedipine- andmibefradil-induced changes in renal microvascular tone
The pretreatment with staurosporine (50 nmol/L)
had no effect on basal arteriolar diameters in WKY(n ¼ 6) or SHR kidneys (n ¼ 6). In the presence ofstaurosporine, ANG II (0.3 nmol/L) caused vasoconstriction of both afferent and efferent arterioles in
WKY and SHR (Fig. 2, ﬁlled bars). Of note, in WKY
the ANG II-induced change in afferent arteriolar diameter did not differ from that in the absence ofstaurosporine (open bars, p > 0.5), whereas blunted
responses were observed in efferent arterioles from
WKY and in afferent and efferent arterioles from SHR(p < 0.05). In this setting, nifedipine dilated the ANG
II-constricted afferent arterioles in a dose-dependent
manner, with greater responsiveness observed in SHR
kidneys at doses of 10 and 100 nmol/L (p < 0.5; Fig. 3,
upper left). No vasodilator effect was observed in theefferent arteriole from WKY or SHR (Fig. 3, upper
right).
In the presence of staurosporine, mibefradil potently
reversed the ANG II-induced constriction of afferent
arterioles in both WKY and SHR (Fig. 3, lower left).
Thus, in the afferent arterioles from SHR, the pretreatment with staurosporine eliminated the attenuated vasodilator responses to mibefradil (see Fig. 1, lower left).
No difference in the vasodilator response to mibefradil
was noted in the efferent arteriole between WKY andSHR (Fig. 3, lower right).
The administration of thapsigargin (1 mmol/L) did
not alter the basal diameters of afferent or efferent
arterioles. In this setting, the vasoconstrictor response
to ANG II was totally abolished in the afferent arterioles from WKY kidneys (1 G 4%, n ¼ 12; Fig. 2,
hatched bars). In the efferent arteriole from WKY,
thapsigargin markedly blunted, but did not eliminate
completely, this response (18 G 3%, n ¼ 12). Similarly, the afferent and efferent arterioles from SHR
kidneys exhibited diminished vasoconstrictor responses
to ANG II (afferent, 9 G 4%; efferent, 22 G 4%;
n ¼ 12). In the presence of thapsigargin, nifedipine had
no effect on arteriolar diameter in WKY or SHR kidneys (Fig. 4, upper). Similarly, mibefradil failed to alter
the arteriolar tone of either vessel (Fig. 4, lower).
Discussion
The present study has demonstrated that nifedipine
causes marked vasodilation of the afferent arteriole,
which is nearly identical in magnitude in WKY andSHR kidneys (Fig. 1). In contrast, the ability of mibefradil to dilate this arteriole differs, with blunted
responsiveness observed in SHR. Since mibefradil elicits relatively selective inhibition on T-type Ca channels,20 the diminished responsiveness of the afferent

106Fig. 4 Effect of nifedipine and mibefradil on angiotensin II-induced
constriction of renal arterioles in the presence of thapsigargin (1mmol/L). In WKY, angiotensin (ANG) II failed to constrict the afferent arterioles. In SHR, ANG II exerted a diminished constrictor
action on afferent/efferent arterioles. Neither nifedipine (upper) or
mibefradil (lower) had any vasodilator effect on renal arteriolar tonein the presence of thapsigargin. Results are means G SEM.

arteriole to mibefradil would be associated with alteredfunction of T-type Ca channels in this vessel in hypertension.4,27 Of interest, in SHR kidneys the mibefradilinduced vasodilation is greater in efferent than inafferent arterioles, whereas nifedipine produces a relatively selective vasodilation of the afferent arteriole(Fig. 1).11,12,14,21 Since systemic hypertension and elevated renal perfusion pressure would elevate myogenic
afferent, but not efferent, arteriolar tone through the Ltype Ca channel-dependent mechanism,21 the blockadeof T-type Ca channels is expected to cause greater dilation of efferent than afferent arterioles in hypertensive
animals. The difference in renal arteriolar action ofthese channel blockers therefore could inﬂuence therenal protective action of L-type and T-type Ca channel
blockers in SHR.28
Renal microvessels possess unique characteristics
with regard to their vasoconstrictor mechanisms. It is
well established that L-type Ca channels prevail predominantly in the afferent arteriole.12–14 Furthermore,
the mechanisms for ANG II-induced vasoconstriction
differ in afferent and efferent arterioles.14 Thus, in
WKY kidneys the effects of staurosporine and thapsigargin on the renal microvessels (i.e., Fig. 2) strongly
suggest that the IP3 production constitutes a major
determinant of the afferent arteriolar tone induced
by ANG II in kidneys from normotensive rats, whereas
the efferent arteriole requires both IP3- and PKC-

Hayashi K, et al: Ca channels and PKC in hypertension

mediated pathways for the ANG II-induced constrictor
response.14 Moreover, the present study shows that theability of staurosporine to inhibit the ANG II-induced
afferent arteriolar constriction is augmented in SHR(Fig. 2). These observations indicate that relative activity of PKC and IP3 pathways is altered in afferent arterioles of SHR, with greater activation of PKC in SHR,
which is consistent with the previous reports by otherinvestigators indicating enhanced PKC activity inaorta29,30 and mesenteric artery30 of hypertensive animals. Of interest, PKC is reported to activate various
biological signaling, including free radical formation31
and Rho-kinase activation.32 Indeed, both free radicals33 and Rho-kinase are demonstrated to be upregulated in SHR.34 These effects of PKC as well as direct
effects on vascular smooth muscles would serve tomodify vascular tone in renal arterioles.
Alterations in PKC activity in hypertension would
modify the responsiveness to Ca channel blockers. In
the present study, we have found that during the treatment with staurosporine, in which PKC is blocked while
the IP3 pathway ostensibly remains intact, nifedipine
exerts greater vasodilator action on the afferent arteriole in SHR than in WKY (Fig. 3). This observationsuggests, although indirectly, that the IP3-mediatedvasoconstrictor component is more sensitive to the vasodilator action of nifedipine in SHR, and therefore may
bear on the issue that L-type Ca channel activity isenhanced in hypertensive animals.3,35 In this regard,
we previously demonstrated that the PKC-mediatedconstrictor tone of the afferent arteriole is relatively
refractory to the blocking action of the L-type Ca
channel blocker.14,15 It might be that the apparently
identical responsiveness of the afferent arteriole tonifedipine (i.e., Fig. 1, upper left) is the overall consequences originating from the attenuated action of
nifedipine on PKC-mediated tone and the enhanced
sensitivity to the L-type Ca channel blockade. Clearly,
it requires further investigations to establish this formulation.
In analogy with the action of nifedipine, the present study demonstrates that the pretreatment withstaurosporine restores the diminished responsiveness tomibefradil observed in afferent arterioles from SHR
kidneys (Figs. 1 and 3). Since staurosporine prevents
the PKC-mediated constrictor mechanism, a substantial
component of the remaining vasoconstrictor tone during ANG II and staurosporine treatment should be an
IP3-mediated Ca release pathway.14,15 Consequently,
it is conjectured that the T-type Ca channel blockadeby mibefradil causes similar degrees of the inhibitionon the IP3-mediated vasoconstrictor tone in WKY and
SHR. Alternatively, to the extent that mibefradil
potently inhibits the IP3-medited constrictor mechanism
but fails to reverse the PKC-mediated vasoconstriction

Keio J Med 2005; 54 (2): 102–108[36; see below], the attenuated vasodilation observed in
SHR kidneys (i.e., Fig. 1) may reﬂect the reminiscenceof the enhanced PKC activity in SHR. Again, theseobserved results are consistent with the formulationthat hypertension alters the PKC activity,29,30 which
would contribute to the enhanced vascular responsiveness in hypertensive animals. Although it remains
undetermined how mibefradil modiﬁes intracellular
vasoconstrictor mechanisms, recent investigations suggest an intimate communication between the plasma
membrane and the endoplasmic reticulum.37 Thus, Ttype Ca channels within the plasma membrane might
affect the sarcoplasmic Ca release. Indeed, T-typechannel activation is reported to facilitate Ca 2þ releasefrom sarcoplasmic reticulum in cardiac myocytes.38
In contrast to the potent vasodilator action of Ca
channel blockers on the arteriolar tone during the PKC
inhibition, these blockers exert less vasodilator action
on renal arteriolar tone induced by PKC activation.
Thus, in the presence of thapsigargin, nifedipine failed
to alter the afferent arteriolar tone induced by ANG II
in SHR (Fig. 4, upper right). Furthermore, mibefradil
had no effect on the ANG II-induced constriction ofrenal arterioles in either WKY or SHR. In this regard,
we have recently demonstrated that the PKC-induced
tone of renal arterioles is resistant to the vasodilator
action of nifedipine14 and mibefradil.36 Collectively,
the differing responsiveness to Ca channel blockers of
PKC and IP3 pathways would determine the vasodilator of these agents in hypertensive animals.
Finally, whether the difference in the experimental
setting affect the renal microvascular responsivenesswarrants comment. Since our results are obtained in theisolated perfused hydronephrotic kidney model, renal
microvascular responsiveness might differ from thatin the normal kidney. In this regard, we previously
demonstrated that the renal microvascular response to
ANP,22 pressure,23 and endothelin39 is qualitatively
identical in isolated normal and hydronephrotic rat
kidneys. Furthermore, the renal microvascular effectsof nifedipine and mibefradil in the isolated perfusedhydronephrotic kidney are similar to those observedin canine renal microvessels using the intravital CCD
videomicroscopic technique.40 Of course, caveat is inorder in interpreting our current observations becausesome intrarenal mechanisms indirectly affecting renal
hemodynamics (i.e., tubuloglomerular feedback) arelacking in the hydronephrotic kidney model.
In conclusion, the present study demonstrates that
L-type (nifedipine) and T-type Ca channel blockers(mibefradil) exert potent vasodilator action on rat renal microvessels. In SHR, however, these actions are
modiﬁes by a PKC-mediated component of the vasculartone on which either T-type or L-type Ca channel
blockers are ineffective. Furthermore, the greater sen-107

sitivity to nifedipine of the afferent arteriole of SHR
kidneys during the treatment with staurosporine suggests that L-type Ca channel activity is augmented in
hypertensive animals. These alterations in renal arteriolar responsiveness in hypertensive animals therefore
would affect the sensitivity of renal arterioles to Ca
channel blockers, and may determine the renal microvascular hemodynamics in hypertension.
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