Vol. 273, Issue 4, H1816-H1823, October 1997
Endogenous nitric oxide on arterial hemodynamics: a comparison
between normotensive and hypertensive rats
Hsing I.
Chen and
Cheng Tao
Hu
Department of Physiology and Cardiovascular Research Laboratory, Tzu
Chi College of Medicine, Hualien; and Institute of Undersea and
Hyperbaric Medicine, National Defense Medical Center, Taipei,
Taiwan, Republic of China
 |
ABSTRACT |
Endogenous nitric oxide (NO) plays an
important role in maintaining a vasodilator tone. In the present study,
we compared the effects of NO blockade on the steady and pulsatile
components of arterial hemodynamics between spontaneously hypertensive
rats (SHR) and normotensive Wistar-Kyoto strain (WKY), 22-26 wk of age. In the first series of experiments, various doses (1-30 mg/kg iv) of NG-nitro-L-arginine methyl
ester (L-NAME) were administered
to block the NO release in anesthetized WKY and SHR. In both WKY and
SHR, L-NAME caused a
dose-dependent increase in arterial pressure (AP) with a decrease in
heart rate (HR). The maximal effects of
L-NAME on AP and HR occurred at
a dose of 10 mg/kg. Both the AP increase and HR decrease were higher in
SHR (AP, +38 ± 4 mmHg; HR, 
49 ± 5 beats/min) than WKY
(AP, +22 ± 3 mmHg; HR, 33 ± 5 beat/min). In other
series, the technique of impedance spectral analysis was employed to
investigate the effects of
L-NAME (10 mg/kg iv) on the
arterial hemodynamics. The aortic pressure and flow waves were recorded
and subjected to Fourier transform for the analysis of impedance
spectra. Both in WKY (n = 12) and in
SHR (n = 12), L-NAME significantly increased
AP and total peripheral resistance (TPR). The pulsatile and
frequency-dependent hemodynamics including characteristic impedance,
wave reflection, and ventricular work were only slightly altered.
Despite higher resting values of AP and TPR in SHR (mean AP, 154 ± 7 mmHg; mean TPR, 204 ± 17 × 103
dyn · s · cm
5)
than WKY (mean AP, 94 ± 6 mmHg; mean TPR, 98 ± 12 × 103
dyn · s · cm5),
the magnitudes of AP and TPR increments after NO blockade were significantly higher in SHR (AP, +37 ± 3 mmHg; TPR, +124 ± 16 × 103
dyn · s · cm5)
than in WKY (AP, +24 ± 3 mmHg; TPR, +45 ± 7 × 103
dyn · s · cm5).
The continuous formation of endogenous NO affects predominantly the AP
and peripheral resistance in both WKY and SHR. The windkessel functions, such as impedance spectra, pulse-wave reflection, and ventricular work, are less affected after NO blockade. In addition, the
effects of NO release on the AP and TPR appear to be enhanced in rats
with established hypertension.
Fourier analysis; arterial impedance
| |
INTRODUCTION |
IT HAS BEEN WELL DOCUMENTED that continuous release of
endogenous nitric oxide (NO) maintains a dilator tone in the vascular tissues (27, 28). In isolated aortic rings (10, 14, 32, 37) and
perfused vascular beds (1, 18, 39, 40), NO blockade with
NG-monomethyl-L-arginine
(L-NMMA) or
NG-nitro-L-arginine methyl ester
(L-NAME) inevitably caused
vasoconstriction. In the whole body, blockade of NO release
significantly caused an increase in systemic arterial pressure (AP)
(34, 36). The increase in AP was accompanied by an increase in vascular
resistance and a decrease in blood flow in various vascular beds
(7-9). There is little doubt that endothelium-derived NO formation
participates in the regulation of systemic blood pressure and regional
blood flow. However, a detailed analysis of the arterial hemodynamics, including the steady and pulsatile components (4, 5, 13, 31) after NO
blockade, has not yet been reported.
Although hypertension is characterized by elevation of AP and
peripheral vascular resistance as well as alterations in the pulsatile
hemodynamics (5, 13), the role of NO in hypertension has not been well
established (3, 23, 26, 27). Despite many studies suggesting impairment
of endothelial function and NO-dependent vasorelaxation in the
hypertensive state (22-24), still other reports provide evidence
against this contention (16, 20, 42, 43).
In the present study, we used the technique of arterial impedance
analysis for a complete assessment of the arterial hemodynamics (4, 5,
13, 31). The purpose was to observe acute effects of NO blockade with
L-NAME on the AP, heart rate
(HR), vascular resistance, cardiac output (CO), arterial impedance,
compliance, pulse-wave reflection, and ventricular work. These changes
were compared between rats with normotension and long-term hypertension to elucidate the role of NO in windkessel and resistance functions and
the functional alterations in hypertension.
| |
MATERIALS AND METHODS |
Animals.
Spontaneously hypertensive rats (SHR) and age-matched normotensive
counterpart Wistar-Kyoto rats (WKY), male in sex, were used in this
study. The animals were supplied by the National Animal Center and then
housed in our environmentally controlled rooms. Tail cuff pressure was
measured twice a week with a photoelectric volume oscillometer (Ueda,
UR-5000). In SHR, the tail cuff pressure, after
reaching a stage of established hypertension
(22-26 wk), was usually >180 mmHg. Repeated measurements in some
SHR did not indicate a tail cuff pressure >180 mmHg, so these rats
were not selected to enter the experiment.
Experimental preparation.
In the first series of experiments, a total of 24 SHR and an equal
number of WKY were used for the dose effects of
L-NAME on the AP and HR. Rats
were anesthetized with pentobarbital sodium (40 mg/kg ip). A
tracheotomy was performed to provide artificial ventilation with a
tidal volume of 3-5 ml and respiratory rate of 50-70
breaths/min. The femoral artery was cannulated for the recording of AP,
and the femoral vein was cannulated for the administration of drugs or
fluids. HR was monitored by a tachometer triggered by the arterial
pulses.
Recording of the aortic pressure and flow waves for the arterial
impedance analysis was carried out in 12 SHR and 12 WKY. After
anesthesia and artificial respiration, the chest was opened through the
left third intercostal space. An electromagnetic flow probe (model 100 series, internal circumference 7-9 mm; Carolina Medical
Electronics, King, NC) was placed around the ascending aorta to measure
the aortic flow. A Millar catheter with one high-fidelity pressure
sensor (model SPR-407, size 2-Fr; Millar Instruments) was used to
measure the aortic pressure. To minimize baseline drift, the catheter
was soaked in saline at room temperature for at least 1 h before
insertion. The Millar catheter was inserted via the isolated right
carotid artery into the ascending aorta until the catheter tip reached
a position just distal to the flow probe. Electrocardiogram (ECG) of
lead II was recorded with a Gould ECG/Biotach amplifier.
The aortic pressure, flow waves, and ECG were continuously monitored
with a polygraph recorder (model 2800S; Gould, Glen Burnie, MD) and
also recorded on a tape recorder (model MR-30; TEAC) at a recording
speed of 4.8 cm/s for off-line analysis. All data were registered after
the pressure and flow signals had become stable for 3-5 min.
Arterial impedance analysis.
The pressure and flow signals were digitized at 1-ms intervals using a
12-bit analog-to-digital converter (model DAP 1200/4; Microstar
Laboratories) interfaced to a personal computer. Selection of signals
(4 consecutive beats at stable state) was made on the basis of recorded
beats with optimal flow-velocity profile and beats with an R-R interval
<5% different from the average value of all recorded beats during a
stable state. Zero flow was assumed to be the value of flow in middle
to late diastole. The largest modulus of this portion of the flow was
considered to be the noise level. The calibration of the flow-velocity
signal was performed after the experiment. The descending aorta was
cannulated and connected to a resistor. The aortic flow was calibrated
by an infusion of heparinized blood (collected from other rats) at
different rates through the aorta. From the digitized flow-velocity
signal, we determined a time-averaged flow velocity for at least 30 separate beats. This mean velocity was converted to volume flow by
multiplying it by the cross-sectional area of the flow probe. The
appropriate calibration factor for each animal was then determined by
matching the CO obtained from the heparinized blood with the mean
outputs calculated from the digitized flow signal. The flowmeter (model 501D; Carolina Medical Electronics) had a frequency response that was
decreased by 3 dB at ~100 Hz. The phase lag was almost linear with
frequency (1.2°/Hz). Appropriate corrections were applied at each
impedance harmonic to take the phase delay into account. All
hemodynamic parameters were calculated beat by beat. The average value
of four beats was obtained for an individual data point.
For each beat, the impedance modulus was the ratio of the aortic
pressure harmonic to the flow harmonic. The flow phase was subtracted
from the pressure phase at each harmonic to yield the impedance phase
angle. Any flow harmonic with a modulus <1.5 times the noise was not
used for impedance calculation. The characteristic impedance
(Zc)
was the average of impedance moduli in the frequency range of
15-45 Hz with coefficients of variation <10%. First zero crossing of impedance phase angle
( f0) was
evaluated by the linear interpolation method (4, 38).
Systolic, diastolic, and mean aortic pressures, HR, stroke volume (SV),
and total peripheral resistance (TPR) were also determined for each
beat. CO was the product of SV and HR. Because of a curvilinear
relationship between pressure and intravascular volume in the arterial
tree, any acute increase in pressure was associated with reduced
compliance (19, 21). The arterial compliance (C) at pressure (P;
systolic, diastolic, or mean aortic) was obtained from the equation
given by Liu et al. (21) for an exponential pressure-volume
relationship
|
(1)
|
where
SV is stroke volume, K is the ratio of total area under the aortic
pressure curve to the diastolic area,
b is the coefficient in the
pressure-volume relationship and is nearly constant for different
arterial segments [0.0131 (0.009) in aortic arch], P*s is the pressure at the time of
incisura, and Pd is the
end-diastolic pressure. Total external power
(Wt),
consisting both of pressure and of kinetic terms for the left
ventricle, was calculated (25). We also evaluated the oscillatory power
(Wo), the
steady power (Ws), and the
ratio of oscillatory to total power
(Wo/ Wt)
as an index for the efficiency with which the pulsatile energy was converted into forward flow. Finally, we decomposed the measured pressure and flow waves into their forward and backward components (41)
|
(2)
|
|
(3)
|
|
(4)
|
|
(5)
|
where
Pm is the measured pressure wave;
Pf and
Pb are the pulse magnitudes of the
forward and backward pressure components, respectively;
m is the
measured flow wave;
and f and
b are the
forward and backward flow-wave components, respectively. Thus the
measured pressure and flow waves are equal to the sum of a forward and
a backward wave. The pulse magnitudes of the forward and backward
components along with the ratio of the backward to the forward
magnitude were used to characterize the wave-reflection properties. All
data and derived hemodynamic parameters were calculated and analyzed by
computer programs developed in our laboratory.
The measurements of aortic pressure and flow with the arterial
impedance analysis in small animals like rats were essentially similar
to those procedures described previously (5, 13, 45). Because the
Millar catheter (size 2-Fr) used in small animals is only equipped with
a pressure sensor for monitoring the aortic pressure, the measurement
of aortic flow requires open-chest surgery to place an electromagnetic
flow probe around the aorta. The procedures caused a fall
in AP as reported in another study (45). How much the surgical
procedures and blood pressure reduction will affect the hemodynamic
data is not certain. Thus we discarded the data in which the fall in AP
was >15 mmHg after thoracotomy and flow-probe placement both in WKY
and in SHR. Although the selection could minimize the effects of
hemodynamic perturbation, the results only pertained to measurements in
the open-chest condition both in WKY and in SHR.
Experimental protocol and statistical analysis.
An NO synthase inhibitor, L-NAME
(Sigma) was used to block the endogenous NO (9, 27, 36). It was
dissolved in saline solution to a concentration of 20 mg/ml. The drug
was delivered intravenously by a slow bolus injection (0.1 ml/5 s).
In the first series of experiment, the optimal doses of
L-NAME for WKY and SHR were
tested. Four doses of L-NAME (1, 5, 10, and 30 mg/kg) were administered intravenously in eight separate groups of WKY (n = 6 for each dose)
and SHR (n = 6 for each dose) to
observe the changes in AP and HR. The dose-response histogram (Fig.
1) indicated that
L-NAME caused a maximal increase
in AP and a decrease in HR at a dose of 10 mg/kg.
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Fig. 1.
Dose effects of NG-nitro-L-arginine
methyl ester (L-NAME) on
arterial pressure (AP) and heart rate (HR). * Significantly
different from corresponding value at previous dose
(P < 0.05);  significant
difference in changes between Wistar-Kyoto rats (WKY) and spontaneously
hypertensive rats (SHR) (P < 0.05).
Note that changes between 10 and 30 mg/kg are not significantly
different (P > 0.01).
|
|
Because of the complexity of arterial impedance analysis, only one dose
(10 mg/kg) was given to WKY (n = 12)
and SHR (n = 12) in the second series
of experiments. Vehicle injection (saline, 0.2-0.5 ml) did not
induce discernible changes. At a steady state (5-15 min) after
L-NAME, the AP and flow wave
were obtained for the analysis of hemodynamic parameters.
The data were expressed as means ± SE. Statistical evaluation of
the dose-response relationship was done with analysis of variance and
Scheffé's test. A paired t-test
was used for comparisons of hemodynamic parameters between the control
and experimental values. Differences were considered significant at
P values <0.05.
| |
RESULTS |
Dose-dependent changes in AP and HR.
In the first series of experiments, the average baseline mean AP values
(MAP) and HR were 96 ± 4 mmHg and 328 ± 5 beats/min in WKY
(n = 24) and 158 ± 6 mmHg and
374 ± 8 beats/min in SHR (n = 24). Both MAP and
mean HR were significantly higher in SHR than WKY.
L-NAME in various doses (1, 5, 10, and 30 mg/kg) caused an increase in AP with a decrease in HR in
both WKY and SHR (Fig. 1). The changes after 1, 5, and 10 mg/kg were
dose dependent (P < 0.01). However,
the pressor and bradycardic responses to a dose of 30 mg/kg were not
different from those to a dose of 10 mg/kg (P > 0.01). Furthermore, both the
pressor and bradycardic effects of
L-NAME (5, 10, and 30 mg/kg)
were significantly greater in SHR than in WKY
(P < 0.05). At a dose of 10 mg/kg,
the increases in AP were 38 ± 4 mmHg in SHR and 22 ± 3 mmHg in
WKY; the decreases in HR were 49 ± 5 beats/min in SHR and 33 ± 5 beats/min in WKY.
Hemodynamics of steady components.
Figure 2 illustrates the recording of
aortic pressure and flow signals in one WKY and one SHR. The measured
and calculated hemodynamic parameters of steady components, including
AP, pulse pressure (PP), HR, SV, CO, and TPR, are summarized in Table
1. L-NAME inevitably caused
increases in AP and TPR both in WKY and in SHR. In particular, TPR was
elevated by 46% in WKY and 61% in SHR. The HR was slightly decreased
by 9% in WKY and 12% in SHR. SV was not significantly changed,
whereas CO was decreased in both groups because of the decrease in HR.
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Fig. 2.
Recording of aortic pressure and flow waves in 1 WKY and 1 SHR after
vehicle injection (left) and after a
dose of L-NAME at 10 mg/kg
(right). Aortic pressure is elevated
both in WKY and in SHR. After
L-NAME, magnitude of flow wave
is slightly decreased, whereas width is slightly increased.
|
|
Hemodynamics of pulsatile components.
Figure 3 illustrates the impedance modulus
and impedance phase in one WKY and one SHR with a vehicle injection and
after L-NAME. In SHR, the
impedance modulus was discernibly elevated in comparison with WKY. In
addition, the phase angle was shifted to the right. However,
L-NAME did not significantly
affect the impedance modulus in SHR after 15 Hz, whereas it slightly
elevated the level in WKY. The impedance phase did not appear to be
changed by L-NAME both in WKY
and in SHR. L-NAME remarkably
increased the impedance modulus only at 0 Hz, which is the value
corresponding to TPR. Table 2 summarizes
the effects of L-NAME on
pulsatile hemodynamics in WKY and SHR.
Zc was slightly
increased by L-NAME in WKY
(+18%) but not in SHR. L-NAME
decreased the arterial compliance (diastolic, systolic, and mean) by
11-12% in WKY and by 19-27% in SHR. Pulse-wave reflection
(expressed as Pb) was slightly
increased in WKY (+13%) and SHR (+14%). Both in WKY and
in SHR, the other parameters including f0,
Wo, and
Ws were not
significantly altered after
L-NAME administration.
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Fig. 3.
Impedance modulus (top) and phase
(bottom) after vehicle injection and
L-NAME (10 mg/kg) in WKY and
SHR. Note marked elevation in impedance modulus at 0 Hz [value
for total peripheral resistance (TPR)] after
L-NAME. Impedance modulus is
much higher, whereas phase is shifted to right in SHR.
L-NAME has little effect on
modulus and phase in SHR. It only slightly elevates impedance modulus
in WKY.
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|
WKY versus SHR.
This and other previous studies (5, 13) showed that SHR had higher AP,
HR, TPR, Zc,
f0,
Wo,
Ws,
Pb, and
Pf than WKY, whereas SV, CO, and
arterial compliance were lower in SHR than in WKY (Tables 1 and 2). The
differences in response to
L-NAME (10 mg/kg) between WKY
and SHR are summarized in Fig. 4. The most striking findings were the higher magnitudes of increase in AP and TPR
(MAP, +37 ± 3 mmHg; TPR, +124 ± 16 × 103
dyn · s · cm5)
in SHR than the corresponding values in WKY (MAP, +26 ± 4 mmHg; TPR, +45 ± 7 × 103
dyn · s · cm5).
It should be noted that the AP and TPR increases in SHR changed from
much higher baseline values in comparison with those in WKY. In the
first series of experiments (Fig. 1), we similarly observed that
L-NAME at 5, 10, and 30 mg/kg
caused higher magnitudes of AP rise in SHR than in WKY. Although the
differences in AP between SHR and WKY were not statistically different
at a dose of 1 mg/kg, the changes in SHR also appeared to be slightly
higher than those in WKY.
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Fig. 4.
Comparison of L-NAME-induced
changes in mean AP (MAP), HR, stroke volume (SV), cardiac output (CO),
TPR, characteristic impedance
(Zc), arterial
compliance at mean pressure
(Cm), and backward pulse wave
(Pb) between WKY and SHR.
Increases in MAP and TPR are significantly higher in SHR than in WKY.
Decreases in HR and CO are also higher in SHR than in WKY. In contrast,
increase in Zc is
greater in WKY than in SHR. * P < 0.05;  P > 0.05 (not
significant).
|
|
In addition to the difference in AP and TPR changes between SHR and
WKY, the decreases in HR and CO were also greater in SHR than in WKY.
On the other hand, the increase in
Zc was higher in
WKY than in SHR (Fig. 4).
| |
DISCUSSION |
Pulsatile and steady hemodynamics.
It has been well documented that the release of NO maintains a dilator
tone in the small arterioles as well as in the aortic segments and
large arteries (1, 10, 14, 18, 27, 28). With respect to the effects on
the arterial resistance, several studies with the measurement of
regional blood flow or with arterial perfusion demonstrated that acute
NO blockade caused a decrease in blood flow and an increase in
resistance in various vascular beds (1, 7-9). In the current
study, we found that L-NAME elevated the TPR by 46 and 61% in WKY and SHR, respectively. The arterial hypertension after
L-NAME was characterized by this
marked increase in TPR with a slight decrease in CO. The reduction in CO was in turn the result of a decrease in HR without a significant change in SV. The vasoconstrictive effect of NO synthase inhibition may
be attributed to blockade of NO release from not only the endothelium
but also the perivascular nitroxidergic nerves. Recent studies in dogs
and monkeys (30, 44) have demonstrated the presence of nerve fibers
containing NO synthase in the arterial wall. This nitroxidergic nervous
system can be activated by a ganglionic stimulant (nicotine) to cause
NO release and vasodilatation. On the other hand, NO synthase
inhibitors and ganglionic blocking agents produce nerve inhibition and
vasoconstriction. The systemic administration of
L-NAME might affect both
endothelium- and nerve-derived NO. However, it has been suggested that
vasodilation mediated by neurogenic NO in rats is not as significant as
that in dogs and monkeys (30, 33).
With respect to the hemodynamics of pulsatile components, we found that
L-NAME increased
Zc in WKY but not
in SHR. Pb was increased in both
groups; however, it should be noted that the changes were relatively
small compared with the big increases in TPR and AP. It was quite
surprising that our results revealed a relatively weak action of
L-NAME on the arterial impedance
and pulse-wave reflection. These pulsatile hemodynamic components reflected mainly the changes of viscoelastic properties of the aorta
and large arteries (4, 5, 13, 25, 31). It appeared that our findings
were somehow not in agreement with the results of many studies in which
NO blockade was shown to cause profound constriction of the aortic
segments and/or large arteries (6, 34, 36, 37). In particular,
Faraci (6) compared the acute effects of NO blockade on the constrictor
responses between large arteries and small arterioles in the cerebral
circulation of anesthetized rats. In a cranial window preparation, he
found that topical application of NO blocker caused contraction of the
large arteries by 10.4%. In contrast, the diameter of the
small arterioles was only reduced by 3.7%. These findings led to a
conclusion that NO release in the cerebral circulation had a greater
influence on basal tone in large arteries than in small arterioles. The
conclusion seems to contradict the results of the present study and
is subject to discussion. First, whether the same finding can be
applied to the other vascular bed is not known. Rees et al. (35)
observed diameter changes in the microcirculation of the hamster cheek pouch. They found that NO caused potent dilation, whereas NO blockade produced strong constriction of the small arterioles (8-35 µm). These findings, taken together with the studies in regional vascular beds (1, 7-10, 14, 18, 37), indicate that NO exerts potent effects
on the arteriolar resistance vessels. Second, because the vascular
resistance is inversely proportional to the fourth power of the radius,
a small constriction in the arterioles can produce a great increase in
the vascular resistance. Finally, it should be noted that the above
experiment (6) was done by topical application of the NO blocker in
different sections of the pial vessels. The results could be different
from those obtained in the whole vascular beds or in systemic
circulation, particularly when NO blocker was given systemically. In
this connection, Griffith and co-workers (11, 12) used the
microangiographic technique to measure the diameter changes in the
perfused rabbit ear arterial system. An intra-arterial infusion instead
of topical application was used for the administration of NO blocker.
They found that constriction was more prominent in small arterioles
than in upstream large arteries. The results indicate that interaction
among various segments occurs in the arterial system. The increase in
perfusion pressure due to downstream vasoconstriction may cause passive dilation and offsets the possible vasoconstriction of the upstream large vessels. Acute NO blockade might have produced some
vasoconstrictive effects on the large windkessel vessels. However, a
possible increase in arterial impedance was counterbalanced by the
increase in diameter of the aorta and large arteries due to a rise in
AP. Because Zc is
inversely related to the aortic lumen (4, 19), an increase in aortic
diameter tends to reduce
Zc.
Arnal et al. (2) recently reported that, after a period (4-8 wk)
of chronic administration of
L-NAME, the rat developed sustained hypertension. However, ventricular hypertrophy was not found
in this model of hypertension. Previous studies from our laboratory (5,
13) demonstrated that the impedance factors were more important than AP
and peripheral resistance in the development of ventricular hypertrophy
after long-term hypertension. The relatively weak action of NO blockade
on the arterial impedance, wave reflection, and ventricular work may be
one of the reasons why ventricular hypertrophy did not develop in the
hypertensive model of chronic NO blockade.
In summary, analysis of the arterial hemodynamics indicates that acute
NO blockade with L-NAME in WKY
and SHR predominantly affects the resistance vessels. The windkessel
functions, pulse-wave reflection and ventricular work, are only
slightly altered.
Normotension versus hypertension.
The current and previous studies (5, 13) revealed that AP, HR, TPR,
Zc, and
Pb were remarkably elevated in SHR
compared with WKY. It was quite surprising that the magnitudes of AP
and TPR increments after L-NAME
were significantly higher in SHR than in WKY (Fig. 3). Similar findings
also occurred in the first series of this experiment (Fig. 1). The rise
of AP in response to L-NAME at
various doses was higher in SHR than in WKY. These observations seem to
be contradictory to the contention that endothelial function is
impaired in hypertension (22-24). However, the involvement of NO
synthesis and release in the hypertensive state remains obscure. An
early study by Konishi and Su (15) revealed that the vasodilatory response of aortic rings to acetylcholine was not impaired in SHR
compared with WKY. On the other hand, the acetylcholine-induced vasodilatation in the segments of femoral artery was greater in SHR
than in WKY. Fozard and Part (7) studied the hemodynamic responses to
NO blockade with various doses of
L-NMMA. They found that the
increases in AP and vascular resistance in renal, carotid, mesenteric,
and hindquarter beds were not different between SHR and WKY. These
findings led to a suggestion that a reduced NO tone in the vasculature
is unlikely to be a major factor contributing to hypertension. Li and
Bukoski (20) also reported that the endothelium-dependent relaxation of
resistance vessels was not impaired in hypertensive rats. Our results
in the present study may further suggest that NO function in the
vascular beds can be enhanced in the hypertensive state and provides a
compensatory mechanism to keep the blood pressure and peripheral
resistance at lower levels. In fact, several recent studies have
provided evidence to indicate that NO release is not impaired but
enhanced in the hypertensive state. Yamazaki et al. (43) and Lacolley et al. (16) reported that NO blockade produced exaggerated pressor response in SHR compared with WKY. The phenomenon of a greater increase
of AP after NO blockade appeared to occur in different ages of SHR
versus WKY: 22-26 wk in the present study and 12-13, 16, and
53-54 wk in other studies (16, 43). In addition, the inhibitory
effects of an NO synthase blocker on the endothelium-dependent relaxation of the aortic rings were greater in hypertensive than in
normotensive rats (17). In the carotid artery, SHR had a lower
compliance than WKY. However, the guanosine 3',5'-cyclic monophosphate (cGMP) content in the arterial wall was much greater in
SHR than in WKY. Removal of the endothelium caused a greater reduction
of cGMP in SHR than in WKY, suggesting the "cGMP pathway" was
more active in SHR compared with WKY (29). Xiao and Pang (42) further
reported that the macrophages and vascular smooth cells from SHR
produced a significantly higher amount of NO compared with those from
WKY. They suggested that a generalized activation of the NO synthesis
system that occurred in SHR may be an important factor contributing to
lymphocyte depression and blood pressure control. These findings are in
agreement with the results of the present study in which we find that
the basal release of NO is not impaired but enhanced in rats with
hypertension. In addition to the AP and vascular resistance, the
decreases in HR and CO were higher in SHR than those in WKY. On the
other hand, the increase in
Zc was lower in
SHR than in WKY.
In summary, our results indicate that the basal release of NO
predominantly affects the resistance functions in both SHR and WKY. The
windkessel functions are only slightly affected. Furthermore, the
effects of NO on the AP and peripheral resistance are not impaired but
enhanced in the hypertensive state.
| |
ACKNOWLEDGEMENTS |
The authors acknowledge the competent technical assistance of C. Y. Wu and W. S. Yang in preparation of this manuscript.
| |
FOOTNOTES |
This work is supported by Grants-in-Aid from the National Science
Council (NSC-85-2331-B320-001 and NSC-86-2314-B-320-013), Tzu Chi
Charity Foundation, and Outstanding Scholarship Development Foundation.
Address for reprint requests: H. I. Chen, Dept. of Physiology, Tzu Chi
College of Medicine, 701, Section 3, Chung Yan Road, Hualien, Taiwan,
ROC.
Received 22 April 1997; accepted in final form 17 June 1997.
| |
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