(Hypertension. 1998;31:1261-1265.)
© 1998 American Heart Association, Inc.
Dietary Sodium Restriction Impairs Endothelial Effect of Insulin
Carmine Vecchione;
Carmine Morisco;
Luigi Fratta;
Luigi Argenziano;
Bruno Trimarco;
; Giuseppe Lembo
From the IRCCS "INM NEUROMED," Pozzilli (IS) (C.V., C.M.,
B.T., G.L.), and the Department of Internal Medicine, School of Medicine,
"Federico II" University, Naples (C.V., L.F., L.A., B.T.), Italy.
Correspondence to Giuseppe Lembo, MD, PhD, IRCCS "INM NEUROMED" Località Camerelle, 86077 Pozzilli (IS), Italy. E-mail glembo{at}connect.it
 |
Abstract
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Abstract—Hyperinsulinemia
and high salt intake represent two independent
cardiovascular risk factors. However, it is still
unknown whether the change in dietary salt intake may affect the
ability of insulin to stimulate whole-body glucose uptake and to
modulate endothelial function. Regarding this latter
issue, we have recently demonstrated that insulin enhances
endothelial-mediated 
2-adrenergic
vasorelaxation. In overnight-fasted, freely moving Wistar-Kyoto rats
(10 to 12 weeks old), we assessed whole-body glucose uptake (in
milligrams per kilogram per minute) during a
euglycemic-hyperinsulinemic clamp (insulin
infusion rate, 3 mU · kg-1 ·
min-1) after 3 weeks of normal (NSD, 2% NaCl), high (HSD,
6% NaCl), and low (LSD, 0.6% NaCl) sodium diet. Three days after the
clamp study, rats were killed to assess 2-adrenergic
vasorelaxation evoked by UK 14,304 (10-9 to
10-6 mol/L) in aortic rings in control conditions and
after insulin exposure (100 µU/mL). Different sodium intakes did not
modify the mean blood pressure or the insulin-stimulated whole-body
glucose uptake (NSD: 14±1.2, n=16; HSD: 15.4±1.7, n=14; LSD:
14.8±0.8, n=14; NS). In contrast, we confirmed the ability of insulin
to enhance 2-adrenergic vasorelaxation during NSD and
HSD (
% of maximal relaxation, NSD: from 32±3% to 58±3.4%, n=9,
P<0.01; HSD: from 33±3.8% to 59±3.5%, n=8,
P<0.01), but this effect was impaired during LSD (%
maximal relaxation, from 36±1.5% to 36±3.4%, n=8, NS). In
conclusion, our data demonstrate that in Wistar-Kyoto rats, changes in
dietary salt intake do not modify the insulin-stimulated whole-body
glucose uptake. In contrast, LSD impairs the insulin potentiation of
2-adrenergic vasorelaxation, thus suggesting that
dietary salt restriction provokes an impairment of insulin effect on
endothelial function.
Key Words: sodium chloride • vasorelaxation • glucose uptake • blood pressure • aortic rings • glucose clamp technique
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Introduction
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Several
epidemiological studies have suggested that distinct factors related to
dietary habits, such as salt intake and insulin, may have a major
impact on blood pressure homeostasis.1 2 3 4 5 6
Actually, both the amount of sodium contained in a dietary regimen and
the physiological rise of the pancreatic hormone in
response to food intake are able to determine profound neuroendocrine
adjustments that can influence the cardiovascular
regulation.7 8 9 So far, the relationship between
salt intake and insulin action has been the object of several studies
that have tried to determine the effect of insulin on sodium
metabolism. In particular, it has been revealed that
insulin affects sodium metabolism by acting on sodium
reabsorption at the renal tubular level.10 In
contrast, it is still unclear whether changes in dietary salt intake
influence insulin action. In this regard, it is known that changes in
sodium intake may produce important consequences on
arterial blood pressure,1 2 3 and this
in turn is inversely related to insulin
sensitivity.11 12 13 To verify whether an
interaction between sodium intake and insulin sensitivity does exist
independently by sodium influence on blood pressure, we examined the
insulin effect in WKY under different sodium diet regimens. This
normotensive rat strain is resistant to blood pressure change
induced by modification of sodium intake. We focused our attention both
on insulin-mediated glucose uptake and on the effect of the hormone on
vascular tone. On this latter issue, rat aortic rings represent
a reliable model to explore the vascular effects of
insulin14–17; in particular, in this system we
have recently demonstrated that the hormone is able to selectively
sensitize the endothelial
2-adrenergic–evoked
vasorelaxation.18
We therefore investigated the effects of three different levels of
sodium diet regimen on insulin-stimulated whole-body glucose uptake and
on insulin modulation of endothelial
2-adrenergic vasorelaxation, which is a target
of insulin vascular action.
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Methods
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Experimental Animals
Most studies were conducted in 69 male WKY (Charles River
Laboratory) aged 10 to 12 weeks. The animals were housed two per cage
and kept in a temperature-controlled room (between 22°C and 24°C)
with a 12-hour light/dark cycle. The animals were divided into three
groups: the first group received an NSD containing 2% NaCl, the second
group received an HSD containing 6% NaCl, and the last group received
an LSD containing 0.6% NaCl (Mucedola, Milan). Food and water were
provided ad libitum. After 2 weeks, the animals were housed
individually in metabolic cages equipped with a drinking
bottle and food cup on the outside of the cage so that urine could be
collected without contamination from food and water (NSD, n=16; HSD,
n=14; LSD, n=14).
The experimental protocol was in accordance with the guidelines of our
institution for research in animals.
Surgical Procedures
Three days before the
euglycemic-hyperinsulinemic clamp study,
all rats were anesthetized with an
intraperitoneal injection of a mixture of
ketamine (80 mg/kg) and xylazine (10 mg/kg), and polyethylene
catheters (PE-50) were inserted into a femoral artery in a femoral
vein. Both catheters were filled with heparinized saline solution (100
µU/mL) and exteriorized subcutaneously at the interscapular area.
After the surgery, the animals were housed in single cages and were
allowed to recover.
Blood Pressure Measurement
Direct intrafemoral arterial pressure was measured
in conscious freely moving rats after an overnight fast. At 8
AM the arterial catheter was connected to a
pressure transducer (Statham P23db) through an extension of
polyethylene (PE-50) tubing. After a resting period of at least 30
minutes, arterial blood pressure and heart rate were
measured in each animal over a 30-minute period and recorded on a
Gould polygraph at a speed of 100 mm/s. Heart rate was obtained
from the arterial pressure pulse.
Euglycemic-Hyperinsulinemic Clamp
Study
On the same day of blood pressure measurement, insulin-mediated
whole-body glucose uptake was determined in freely moving rats with the
euglycemic-hyperinsulinemic clamp
technique.19 Insulin dissolved in rat plasma was
administered through the femoral vein with an infusion pump at the dose
of 3 mU · kg-1 ·
min-1 for 2 hours. Arterial blood
glucose levels were measured twice in 15 minutes before the clamp study
at 10-minute intervals during the insulin infusion. To maintain basal
glucose levels, a glucose solution (33%) was infused at variable
rates in the same femoral vein, according to the plasma glucose
concentration. Plasma insulin levels were measured at the beginning and
after 120 minutes of insulin infusion.
Studies on Aortic Rings
On the day of experiments on vascular function, the rats were
weighed and then decapitated. The thoracic aorta was dissected out from
each rat and placed in cold Krebs-Henseleit bicarbonate buffer solution
with the following composition (mmol/L): NaCl 118.3, KCl 4.7,
CaCl2 2.5, MgSO4 ·
7H2O 1.2,
KH2PO4 1.2,
NaHCO3 25, and glucose 5.6. The aorta was cleaned
of the adhering perivascular tissue and cut into rings 3 mm long.
Aortic rings were suspended in isolated tissue baths filled with 20 mL
Krebs' solution continuously bubbled with a mixture of 5%
CO2/95% O2 (pH 7.37 to
7.42) at 37°C. One end of the aortic ring was connected to a tissue
holder and the other to an isometric force transducer. The signal was
passed to a Gould pressure processor and then acquired in a
computerized system with Gould's DASA (Data Acquisition and Signal
Analysis). The analysis of the generated curves was
performed with View II software (Gould Instruments), and the
sensitivity of the system was 5±1 mg of tension generated. The rings
were equilibrated for 90 minutes in the unstretched condition, and the
buffer was replaced every 20 minutes. The length of the smooth muscle
was increased stepwise in the equilibration period to adjust passive
wall tension to 2 g. This tension was found optimal for
contractions of aorta from WKY by testing the contractions to
norepinephrine (10-3 mol/L). Once
the basal tension was established, the length of the rings was not
altered thereafter.
The following drugs were used: acetylcholine, phenylephrine
(Sigma Chemical Co), UK 14,304 (Research Biochemicals International),
and sodium nitroprusside (Malesci). Drugs were prepared daily in
distilled water. Concentrations of the drugs are reported as the final
molar concentration in the organ bath.
To verify whether changes in sodium intake may affect
endothelial or smooth muscle relaxations per se,
dose-response curves to acetylcholine (10-8 to
5 · 10-5 mol/L), UK 14,304
(10-9 to 5 · 10-6
mol/L [a selective 2-agonist]), and sodium
nitroprusside (10-9 to
10-7 mol/L) were performed in vessels
precontracted with phenylephrine
(10-6 mol/L). Because relaxations induced by UK
14,304 have been demonstrated to be the targets of vascular insulin
action, dose-response curves to UK 14,304 were repeated after 30
minutes of exposure to human regular insulin (100 µU/mL). This dose
was chosen to reproduce levels of the hormone commonly observed in
pathophysiological conditions associated with
insulin resistance. Moreover, previous studies have revealed that
higher levels of insulin do not show any difference from that used in
the present study.18
Plasma Glucose, Plasma Insulin, and Serum and Urinary
Sodium
Sodium concentration in urine was measured by an
autoanalyzer (Beckman System E2A). Plasma glucose concentration
was determined by the glucose oxidase method (Beckman Glucose
Analyzer). Plasma insulin was measured by radioimmunoassay
(Incstar).
Statistical Analysis
Data are expressed as mean±SE. Vasorelaxation evoked by UK
14,304, acetylcholine, and sodium nitroprusside is expressed as percent
inhibition of the contraction evoked by phenylephrine.
Concentration of vasorelaxant agonists producing half maximal
inhibition of the phenylephrine contractile effect
(ED50) and maximum relaxation effect were
estimated by nonlinear regression analysis from log
concentration-response curves and expressed as
ED50 and percent maximal relaxation (GraphPad
Prism).
Statistical evaluation of the data was carried out by two-way ANOVA
with Bonferroni's t test for multiple comparisons and
Student's t test. Differences were considered to be
statistically significant at P<0.05.
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Results
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Urinary Na+ and K+ Excretion, Body Weight,
Blood Pressure, Plasma Glucose, and Plasma Insulin
As expected, the different sodium regimens were able to modify
urinary sodium excretion. In particular, during HSD the sodium
excretion was eightfold greater than that measured during LSD
(20 935±2330 versus 2648±352 µmol/24 h, P<0.01)
in keeping with the change in dietary sodium calculated by food intake.
The sodium excretion of rats receiving NSD was 3890±489 µmol/24
h, significantly different from excretion observed during HSD and LSD,
but the magnitude of these changes did not strictly correspond to that
expected, likely reflecting a diverse appetite for food at this level
of salt intake.20 In contrast, the urinary
potassium excretion was not significantly affected by change in sodium
diet regimen (NSD, 3117±414 µmol/24 h; HSD, 3401±253
µmol/24 h; LSD, 2907±181 µmol/24 h; NS).
After 3 weeks, body weight was 325±5 g in the group treated with NSD
and was not significantly different from that measured during both HSD
(334±2 g) and LSD (314±9 g), respectively. However, the body weight
of the HSD group was significantly higher (P<0.01) than
that observed in the LSD group. Furthermore, arterial blood
pressure (mean blood pressure [mm Hg]: NSD, 127±7; HSD, 124±1;
LSD, 129±4; NS), glucose ([mmol/L] NSD, 5.38±0.2; HSD, 5.33±0.1;
LSD, 5.45±0.1; NS), and insulin plasma levels ([pmol/L] NSD,
214±14; HSD, 193±14; LSD, 208±22; NS) were similar in the three
study groups.
Euglycemic-Hyperinsulinemic Clamp
Study
As shown in Table 1
,
plasma insulin levels increased in the high
physiological range during the clamp study, while
glucose levels were maintained adequately at their basal values in all
study groups. In addition, the rate of glucose infusion required to
maintain euglycemia during the different sodium diet regimens was
comparable, suggesting that change in sodium intake does not influence
the insulin-stimulated glucose consumption.
Studies on Aortic Rings
Cumulative addition of phenylephrine to the muscle
bath caused contractions in all aortic segments, revealing a good
general responsiveness of the vessels used for further investigations.
The tension developed by phenylephrine
(10-6 mol/L) in the various series of
experiments was not affected by the different sodium diet regimens
(NSD, 1380±40 mg; HSD, 1344±48 mg; LSD, 1343±29 mg; NS).
Furthermore, phenylephrine-evoked contractions were not
influenced by insulin exposure (NSD, 1429±92 versus 1359±93 mg, n=9,
NS; HSD, 1390±102 versus 1322±92 mg, n=8, NS; LSD, 1338±74 versus
1387±59 mg, n=8, NS).
As shown in Figure 1, acetylcholine and
sodium nitroprusside produced concentration-dependent relaxations on
aortic rings, and more important, the different sodium regimens were
not able to modify the vasorelaxant responses evoked by these agonists
(ED50 for acetylcholine: NSD, 9.09 ·
10-8±3 · 10-8
mol/L, n=9; HSD, 8.34 · 10-8±3 ·
10-8 mol/L, n=8; LSD, 8.42 ·
10-8±2 · 10-8
mol/L, n=8 [NS]; ED50 for sodium nitroprusside:
NSD, 1.02 · 10-8±6 ·
10-9 mol/L, n=9; HSD, 1.45 ·
10-8±2 · 10-9
mol/L, n=8; LSD, 1.16 · 10-8±1 ·
10-9 mol/L, n=8 [NS]).
Similarly, changes in dietary sodium intake failed to modify the
vasorelaxation induced by UK 14,304, but they were able to interfere
with the effect of insulin on this endothelial
response. In particular, as expected, insulin exposure was able to
potentiate 2-adrenergic vasorelaxation in rats
receiving an NSD, and this sensitizing effect of the hormone was
comparable in magnitude in the group that received HSD. In contrast,
insulin did not modify the vasorelaxation evoked by UK 14,304 in the
LSD group (Figure 2 and Table 2).
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Discussion
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In this study, we explored the effect of change in sodium intake
on two important targets of insulin action: the stimulation of
whole-body glucose uptake and the modulation of vascular
endothelial function. Our results clearly demonstrate
that in normotensive WKY, changes in sodium diet regimens are not able
to influence the effect of physiological insulin
levels on whole-body glucose uptake. In contrast, dietary salt
restriction abolishes the insulin sensitization of
2-adrenergic vasorelaxation exhibited at
normal and high dietary sodium intake.
The mechanism by which low salt diet impairs the insulin
effect on vascular function has yet to be clarified. We have recently
reported that insulin affects heterogeneously
endothelium-dependent relaxations. Specifically, the
hormone amplifies the 2-adrenergic pathway,
while it does not interfere with other
endothelial-mediated responses.18
A potential explanation of the effect of dietary salt restriction on
insulin sensitization of 2-adrenergic
vasorelaxation may be a general impairment of
endothelial function. On this issue, our results
clearly demonstrate that changes in dietary sodium regimens are unable
to affect the whole endothelial vasorelaxation. This
suggests that low sodium intake selectively influences insulin action
on endothelial function. The hypothesis that dietary
salt restriction may modify insulin receptor signal does not seem
appropriate because, in our work, low salt diet does not interfere with
insulin-mediated skeletal muscle glucose uptake, which has an insulin
receptor signal transduction pathway similar to the
endothelial ones. However, the intracellular molecular
events generated by insulin receptor activation, which allow the
insulin sensitization of 2-adrenergic
endothelial vasorelaxation, may have distinct features
compared with the molecular transduction for the insulin action on the
intermediary metabolism. Thus, low salt intake may
specifically interact with insulin postreceptor molecular events, which
account for insulin vascular action. In this regard, our data do not
allow any definitive conclusion, but a recent
study21 demonstrating in young normotensive
subjects that low sodium intake reduces the vasorelaxant effect of
insulin may lend further support to this hypothesis.
Our conclusions on insulin-stimulated glucose uptake during different
sodium diet regimens are not limited by a recent report by Sechi et
al,22 which demonstrated in the same rat strain
that an increase in dietary salt intake impairs insulin-stimulated
glucose utilization. Their study is not comparable to ours because they
used a more pronounced high salt diet and performed the clamp technique
in anesthetized rats. On the other hand, there is also evidence
in humans indicating that dietary NaCl restriction evokes a
hyperinsulinemic response,23
whereas dietary salt load decreases plasma insulin
levels,24 suggesting that dietary salt intake may
affect insulin sensitivity. It is important to note that in these
latter studies, the measure of insulin sensitivity was mainly derived
from the plasma levels of insulin, which is only an indirect index of
the insulin sensitivity, whereas in our study, the insulin sensitivity
was measured by hyperinsulinemic-euglycemic
clamp technique.
A potential limitation of our study is that we explored the whole-body
glucose uptake under the stimulation of a single insulin dose, which
was titrated to reach levels of hormone close to those observed
postprandially. Therefore, we cannot exclude the possibility that
pharmacological insulin levels mediating the maximum glucose disposal
might be differently regulated by sodium intake. However, it has to be
considered that spontaneously hypertensive rats show their insulin
resistance when physiological levels of the
pancreatic hormone are tested, whereas no difference in
insulin-stimulated whole-body glucose uptake is evident at high
pharmacological levels of insulin.25 A further
potential limitation is that our study population was restricted to
male rats, and therefore our conclusions cannot be broadened to
females. On this issue, it has been reported that the effects of
insulin on vascular function are more pronounced in females than in
males, suggesting that sex hormones can in some manner affect insulin
vascular action.26 Furthermore, estrogens
positively influence endothelial
function,27 which is also the target of the
vascular effects of insulin. For these reasons, to examine the
interaction between sodium intake and insulin-mediated effects, we
decided to study only male rats to make an evaluation without
confounding factors such as sex hormones.
It is known that dietary sodium restriction causes a reduction of
cardiac output and a simultaneous increase of vascular
resistance, and the latter represents the mechanism by which
blood pressure is adequately maintained. Several neuroendocrine factors
sustain the increase of vascular resistance during low salt diet
regimens, and we can speculate that in this latter condition, the lack
of insulin vasorelaxant effect in this condition may contribute to the
increase in vascular tone. In other words, the impairment of vascular
effects of insulin may represent one of the
physiological events that are involved during
dietary sodium restriction and play a role in blood pressure
homeostasis.
It is noteworthy to remember that we recently
reported15 18 that in a genetic model of
hypertension such as spontaneously hypertensive rats, the impairment of
insulin vascular action is present also during the NSD regimen.
This abnormal recruitment of a vascular mechanism present in
normotensives only during sodium restriction may play a contributory
role in the development of hypertension.
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Selected Abbreviations and Acronyms
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| HSD |
= |
high sodium diet |
| LSD |
= |
low sodium diet |
| NSD |
= |
normal sodium diet |
| WKY |
= |
Wistar-Kyoto rat(s) |
|
Received November 20, 1997;
first decision December 9, 1997;
accepted January 19, 1998.
|
References
|
|---|
1.
Weinberger MH. Sodium sensitivity of blood
pressure. Curr Opin Nephrol Hypertens. 1993;2:935–939.[Medline]
[Order article via Infotrieve]
2.
Retting R, Ganten D, Luft FC. Salt and
Hypertension. Berlin, Germany: Springer-Verlag; 1989.
3.
Tobian L. Dietary sodium chloride and potassium have
effects on the pathophysiology of hypertension in humans and animals.
Am J Clin Nutr. 1997;65(suppl):606S–611S.
4.
Reaven GM. Insulin resistance,
hyperinsulinemia and
hypertriglyceridemia in the etiology and
clinical course of hypertension. Am J Med.
1991;90(suppl 2):7–12.
5.
Sowers JR. Insulin and insulin-like growth factor in
normal and pathological cardiovascular physiology.
Hypertension. 1997;29:691–699.[Free Full Text]
6.
Welborn TA, Breckenridge A, Rubinstein AH, Dollery CT,
Fraser TR. Serum insulin in essential hypertension and in
peripheral vascular diseases. Lancet. 1966;1:1336–1337.[Medline]
[Order article via Infotrieve]
7.
Mark AL. Sympathetic neural contribution to
salt-induced hypertension in Dahl rats. Hypertension.
1991;17(suppl I):I-86–I-90.
8.
Trimarco B, Lembo G, Ricciardelli B, De Luca N,
Rendina V, Condorelli GL, Volpe M. Salt-induced plasticity in
cardiopulmonary baroreceptor reflexes in salt-resistant
hypertensive patients. Hypertension. 1991;18:483–493.[Abstract/Free Full Text]
9.
Lembo G, Napoli R, Capaldo B, Rendina V, Iaccarino G,
Volpe M, Trimarco B, Saccà L. Abnormal sympathetic overactivity
evoked by insulin in the skeletal muscle of patients with essential
hypertension. J Clin Invest. 1992;90:24–29.
10.
Rocchini AP, Key J, Bondie D, Chico R, Moorehead C,
Katch V, Martin M. The effect of weight loss on the sensitivity of
blood pressure to sodium in obese adolescents. N Engl J
Med. 1989;321:580–585.[Abstract]
11.
Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA,
Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S. Insulin
resistance in essential hypertension. N Engl J
Med. 1987;317:350–357.[Abstract]
12.
Fournier AM, Gadia MT, Kubrusly DB, Skyler JS, Sosenko
JM. Blood pressure, insulin, and glycemia in non-diabetic subjects.
Am J Med. 1986;80:861–864.[Medline]
[Order article via Infotrieve]
13.
Rose HG, Yallow RS, Schweitzer P, Schwartz E. Insulin
as a potential factor influencing blood pressure in amputees.
Hypertension. 1986;8:793–800.[Abstract/Free Full Text]
14.
Wu H, Jeng YY, Yue C, Chyu KY, Hsueh W, Chan T.
Endothelial-dependent vascular effects of insulin and
insulin-like growth factor I in the perfused rat mesenteric artery and
aortic ring. Diabetes. 1994;43:1027–1032.[Abstract]
15.
Lembo G, Iaccarino G, Vecchione C, Rendina V, Trimarco
B. Insulin modulation of vascular reactivity is already impaired in
prehypertensive SHR. Hypertension. 1995;26:290–293.[Abstract/Free Full Text]
16.
Gros R, Borkowski KR, Feldman RD. Human
insulin-mediated enhancement of vascular ß-adrenergic
responsiveness. Hypertension. 1994;23:551–555.[Abstract/Free Full Text]
17.
Kotchen TA, Zhang HY, Reddy S, Hoffmann RG. Effect of
pioglitazone on vascular reactivity in vivo and in vitro. Am
J Physiol. 1996;270(3 pt 2):R660–R666.
18.
Lembo G, Iaccarino G, Vecchione C, Barbato E, Parrella
L, Morisco C, Monti F, Trimarco B. Insulin selectively enhances
endothelial 2-adrenergic
vasorelaxation through a pertussis toxin-sensitive mechanism.
Hypertension. 1997;30:1128–1134.[Abstract/Free Full Text]
19.
De Fronzo RA, Tobin JD, Andres R. Glucose clamp
technique: a method for quantifying insulin secretion and resistance.
Am J Physiol. 1979;273:E214–E223.
20.
Muntzel M, Pouzet B, Lacour B, Hannedouche T, Drueke T.
Selective effects of sodium and chloride depletion on salt appetite
rats. Am J Physiol. 1991;261(3 pt 2):R603–R608.
21.
Feldman RD, Logan AG, Schmidt ND. Dietary salt
restriction increases vascular insulin resistance. Clin Pharmacol
Ther. 1996;60:444–451.[Medline]
[Order article via Infotrieve]
22.
Sechi LA, Griffin AC, Giacchetti G, Zingara L, Catena
C, Bartoli E, Schambelan M. Abnormalities of insulin receptor in
spontaneously hypertensive rats. Hypertension. 1996;27:955–961.[Abstract/Free Full Text]
23.
Egan BM, Weder AB, Petrin J, Hoffman RG. Neurohumoral
and metabolic effects of short-term dietary NaCl
restriction in man. Am J Hypertens. 1991;4:416–421.[Medline]
[Order article via Infotrieve]
24.
Goodfriend TL, Ball LD, Weinberger MH, Moore TJ, Weder
AB, Egan BM. Salt loads raise plasma fatty acids and lower insulin.
Hypertension. 1991;17:958–964.[Abstract/Free Full Text]
25.
Pitre M, Nadeau A, Bachelard H. Insulin sensitivity and
hemodynamic responses to insulin in Wistar-Kyoto and
spontaneously hypertensive rats. Am J Physiol.
1996;271(Endocrinol Metab 34):E658–E668.
26.
Peuler JD, Johnson BA, Phare SM, Sowers JR.
Sex-specific effects of an insulin secretagogue in stroke-prone
hypertensive rats. Hypertension. 1993;22:214–220.[Abstract/Free Full Text]
27.
Pinto S, Virdis A, Ghiadoni L, Bernini G, Lombardo M,
Petraglia F, Genazzani AR, Taddei S, Salvetti A. Endogenous
estrogen and acetylcholine-induced vasodilation in normotensive women.
Hypertension. 1997;29(pt 2):268–273.
Top
Abstract
Introduction
, n=9), high
(
, n=8), and low (
, n=8) salt diets.
) and during exposure to 100 µU/mL regular insulin (
) in
aortic rings from WKY treated with normal (n=9), high (n=8), and low
(n=8) salt diets. *P<0.01 compared with control
conditions.