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Joey P Granger

Publications and source records attributed to Joey P Granger.

15 recordsLinked to original sources
PubMed2003

Role of reactive oxygen species in endothelin-induced hypertension.

Recent reports have indicated that endothelin-induced vasoconstriction in isolated aortic vascular rings may be mediated by the production of superoxide anion. The purpose of this study was to determine the role of superoxide anion in mediating the chronic renal and hypertensive actions of endothelin. Endothelin-1 (5 pmol/kg per minute) was chronically infused into the jugular vein by use of mini-osmotic pump for 9 days in male Sprague-Dawley rats and in rats treated with the superoxide anion scavenger tempol (30 mg/kg per day). Mean arterial pressure in the endothelin-1-treated rats was 141+/-3 mm Hg, compared with 125+/-2 mm Hg in control rats. Endothelin-1 increased renal vascular resistance (15.3+/-2.5 versus 10+/-1.3 mm Hg/mL per minute) and decreased renal plasma flow (6.5+/-0.9 versus 8.7+/-0.7 mL/min) in control rats. Endothelin-1 also significantly increased TBARS in the kidney and urinary 8-isoprostaglandin F2alpha excretion. The increase in arterial pressure in response to endothelin-1 was completely abolished by tempol (127+/-4 versus 127+/-4 mm Hg). Tempol also markedly attenuated the renal plasma flow and renal vascular resistance response to endothelin-1. Tempol also significantly decreased the level of 8-isoprostaglandin F2alpha in the endothelin-1-treated rats. Tempol had no effect on arterial pressure or renal hemodynamics in control rats. These data indicate that formation of reactive oxygen species may play an important role in mediating hypertension induced by chronic elevations in endothelin.

Animals↗
PubMed2003

Evaluation of a rat model of preeclampsia for HELLP syndrome characteristics.

OBJECTIVE: To determine whether a rat model of preeclampsia includes features consistent with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. METHODS: Preeclampsia was induced experimentally in timed-pregnant Sprague-Dawley rats using the reduced uterine perfusion pressure (RUPP) model. On day 14 of gestation, silver clips were placed around the aorta below the renal arteries and on the left and right uterine arcade at the ovarian artery. All animals were chronically instrumented to determine conscious blood pressure and to obtain blood samples for analysis of complete blood count, platelet count, liver function tests, uric acid, creatinine, and albumin. Blood samples were collected and animals sacrificed on day 19 of gestation, at which time placental and pup weight were obtained. A control group was analyzed similarly. Statistical analysis was performed with the Student t test. RESULTS: The RUPP model animals (n = 8), when compared with the normotensive controls (n = 9), did not show a statistically significant difference in hemoglobin, platelets, liver function tests, uric acid, creatinine, or albumin, although the mean arterial pressure was higher (mean +/- SD 131.9 +/- 17.1 mmHg versus 104.0 +/- 14.0 mmHg, respectively; P = .003) and pup number was lower (RUPP 6.6 +/- 2.4 versus control 13.8 +/- 2.3, P < .001). CONCLUSION: Although decreased uteroplacental perfusion induces changes similar to symptoms of preeclampsia, the RUPP rat model does not appear to express features of HELLP syndrome.

Animals↗
PubMed2003

Endothelin.

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Animals↗
PubMed2002

Endothelin-induced increases in Ca2+ entry mechanisms of vascular contraction are enhanced during high-salt diet.

High-salt diet is often associated with increases in arterial pressure, and a role for endothelin (ET)-1 in salt-sensitive hypertension has been suggested; however, the vascular mechanisms involved are unclear. We investigated whether ET increases the sensitivity of the mechanisms of vascular contraction to changes in dietary salt intake. Active stress and 45Ca2+ influx were measured in endothelium-denuded aortic strips of male Sprague-Dawley rats not treated or chronically infused intravenously with ET (5 pmol/kg per minute) and fed either normal-sodium diet (NS, 1%) or high-sodium diet (HS, 8%) for 9 days. Phenylephrine (Phe) caused increases in active stress that were similar in NS and HS, but were greater in NS/ET (maximum, 10.5+/-0.7) than in NS (maximum, 7.4+/-0.9) rats, and further enhanced in HS/ET (maximum, 14.4+/-1.1) compared with HS rats (maximum, 8.0+/-0.8 x 10(4)N/m2). Phe was more potent in causing contraction in NS/ET than in NS rats and in HS/ET than in HS rats. In Ca2+-free (2 mmol/L EGTA) Krebs, stimulation of intracellular Ca2+ release by Phe (10(-5) mol/L) or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. In contrast, membrane depolarization by high-KCl solution, which stimulates Ca2+ entry from the extracellular space, caused greater contraction in ET-infused rats, particularly those on HS diet. Phe (10(-5) mol/L) caused an increase in 45Ca2+ influx that was greater in NS/ET (27.9+/-1.7) than in NS (20.1+/-1.8) rats and further enhanced in HS/ET (35.2+/-1.8) compared with HS rats (21.8+/-1.9 micromol/kg/min). The Phe-induced 45Ca2+ influx-stress relation was not different between NS and HS rats, but was enhanced in ET-infused rats particularly those on HS. The enhancement of the 45Ca2+ influx-active stress relation in ET-infused rats was not observed in vascular strips treated with the protein kinase C inhibitor GF109203X or calphostin C (10(-6) mol/L). Thus, low-dose infusion of ET, particularly during HS, is associated with increased vascular reactivity that involves Ca2+ entry from the extracellular space, but not Ca2+ release from the intracellular stores. The ET-induced enhancement of the Ca2+ influx-stress relation particularly during HS suggests activation of other mechanisms in addition to Ca2+ entry, possibly involving protein kinase C. The results suggest that ET increases the sensitivity of the mechanisms of vascular smooth muscle contraction to high dietary salt intake and may, in part, explain the possible role of ET in salt-sensitive hypertension.

Adrenergic alpha-Agonists↗
PubMed2002

Enhanced [Ca2+]i in renal arterial smooth muscle cells of pregnant rats with reduced uterine perfusion pressure.

Reduction of uterine perfusion pressure (RUPP) during late pregnancy has been suggested to trigger increases in renal vascular resistance and lead to hypertension of pregnancy. We investigated whether the increased renal vascular resistance associated with RUPP in late pregnancy reflects increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) and contraction of renal arterial smooth muscle. Single smooth muscle cells were isolated from renal interlobular arteries of normal pregnant Sprague-Dawley rats and a rat model of RUPP during late pregnancy. The cells were loaded with fura 2 and both cell length and [Ca(2+)](i) were measured. In cells of normal pregnant rats incubated in Hanks' solution (1 mM Ca(2+)), ANG II (10(-7) M) caused an initial increase in [Ca(2+)](i) to 414 +/- 13 nM, a maintained increase to 149 +/- 8 nM, and 21 +/- 1% cell contraction. In RUPP rats, the initial ANG II-induced [Ca(2+)](i) (431 +/- 18 nM) was not different from pregnant rats, but both the maintained [Ca(2+)](i) (225 +/- 9 nM) and cell contraction (48 +/- 2%) were increased. Membrane depolarization by 51 mM KCl and the Ca(2+) channel agonist BAY K 8644 (10(-6) M), which stimulate Ca(2+) entry from the extracellular space, caused maintained increases in [Ca(2+)](i) and cell contraction that were greater in RUPP rats than control pregnant rats. In Ca(2+)-free (2 mM EGTA) Hanks' solution, the ANG II- and caffeine (10 mM)-induced [Ca(2+)](i) transient and cell contraction were not different between normal pregnant and RUPP rats, suggesting no difference in Ca(2+) release from the intracellular stores. The enhanced maintained ANG II-, KCl- and BAY K 8644-induced [Ca(2+)](i) and cell contraction in RUPP rats compared with normal pregnant rats suggest enhanced Ca(2+) entry mechanisms of smooth muscle contraction in resistance renal arteries and may explain the increased renal vascular resistance associated with hypertension of pregnancy.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2002

Mechanisms of pressure natriuresis.

A central component of the feedback system for long-term control of arterial pressure is the pressure-natriuresis mechanism, whereby increases in renal perfusion pressure lead to decreases in sodium reabsorption and increases in sodium excretion. The specific intrarenal mechanism for the decrease in tubular reabsorption in response to increases in renal perfusion pressure appears to be related to increases in hemodynamic factors such as medullary blood flow and renal interstitial hydrostatic pressure (RIHP), and renal autocoids such as nitric oxide, prostaglandins, kinins, and angiotensin II. Increases in renal perfusion pressure are associated with significant increases in RIHP, nitric oxide, prostaglandin E2, and kinins, and decreases in angiotensin II. The mechanism whereby RIHP increases in the absence of discernible changes in whole kidney renal blood flow and peritubular capillary hydrostatic and/or oncotic pressures may be related to increases in renal medullary flow as a result of nitric oxide-induced reductions in renal medullary vascular resistance. Several lines of investigation support an important quantitative role for RIHP in mediating pressure natriuresis. Preventing RIHP from increasing in response to increases in renal perfusion pressure markedly attenuates pressure natriuresis. Furthermore, direct increases in RIHP, comparable to increases measured in response to increases in renal perfusion pressure, have been shown to significantly decrease tubular reabsorption of sodium in the proximal tubule and increase sodium excretion. The exact mechanism whereby RIHP influences tubular reabsorption is unknown, but may be related to alterations in tight junctional permeability to sodium in proximal tubules, redistribution of apical sodium transporters, and/or release of renal autacoids such as prostaglandin E2.

Blood Pressure↗
PubMed2002

Tumor necrosis factor-alpha-induced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression.

BACKGROUND: Preeclampsia is associated with increases in plasma levels of tumor necrosis factor-alpha (TNF-alpha), a cytokine known to contribute to endothelial dysfunction. We recently reported that a twofold elevation in plasma TNF-alpha produces significant reductions in renal function and hypertension in pregnant rats. The purpose of this study was to determine the role of the nitric oxide (NO) system in TNF-alpha-induced hypertension in pregnant rats. METHODS: Tumor necrosis factor-alpha (50 ng/day) was chronically infused starting at day 14 of gestation. Mean arterial pressure, 24-h urinary nitrite/nitrate excretion, and renal nitric oxide synthase (NOS) protein expression by Western blot analysis was measured at day 19 of gestation. RESULTS: A twofold increase in plasma TNF-alpha levels in pregnant rats resulted in a significant increase in arterial pressure (97 +/- 3.6 v 116 +/- 2.1 mm Hg, pregnant versus TNF-alpha pregnant, respectively, P < .05), but no significant change in urinary nitrite/nitrate excretion (22.0 +/- 1.9 v 20.8 +/- 2.5 micromol/24 h, pregnant versus TNF-alpha pregnant, respectively), a measure of whole body NO production. As abnormalities in renal production of NO would not be reflected in the measure of whole body NO production, changes in renal NOS protein levels were determined. The protein expression of both neuronal (nNOS) and inducible (iNOS) nitric oxide synthase were significantly decreased in the medulla of TNF-alpha pregnant rats (nNOS: 10.6 +/- 0.7 v 8.2 +/- 0.8 densitometric units, P < .05; and iNOS: 19.2 +/- 0.9 v 15.4 +/- 0.8 densitometric units, P < .05, pregnant versus TNF-alpha pregnant, respectively). CONCLUSION: The hypertension associated with a chronic twofold increase in TNF-alpha in pregnant rats is associated with significant decreases in renal nNOS and iNOS protein production.

Animals↗
PubMed2002

Enhanced thromboxane synthesis during chronic reductions in uterine perfusion pressure in pregnant rats.

BACKGROUND: The purpose of this study was to determine the role of thromboxane A2 (TXA2) in a conscious, chronically instrumented rat model of pregnancy-induced hypertension (PIH) produced by chronic reductions in uterine perfusion pressure (RUPP). METHODS: Mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and 24-h urinary excretion of TXB2 (metabolite of TXA2) were determined in normal pregnant rats and RUPP pregnant rats. RESULTS: At day 20 of pregnancy, RUPP rats showed a significantly (P < .05) higher MAP (125 +/- 3 mm Hg v 100 +/- 2 mm Hg) as compared with normal pregnant controls. The elevation in arterial pressure in RUPP group was associated with a marked increase (P < .05) in the urinary concentration of TXB2 compared with normal pregnant group (3663 +/- 488 v 2646 +/- 257 pg/24 h). Baseline GFR (1.74 +/- 0.13 v 2.40 +/- 0.20 mL/min, respectively, P < .05) and ERPF (5.13 +/- 0.44 v 6.44 +/- 0.58 mL/min, respectively) were decreased in RUPP rats relative to pregnant controls. Infusion of a TX receptor antagonist, SQ 29,548 (2 mg/kg bolus plus 2 mg/kg per h infusion) had no significant effect on increased MAP in RUPP pregnant rats. Similarly, ERPF and GFR did not change during acute blockade of TXA2 receptors in this group. CONCLUSION: These findings suggest that enhanced production of TXA2 does not play a major role in mediating the hypertension and renal vasoconstriction produced by chronic RUPP in pregnant rats.

Animals↗
PubMed2002

Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction.

Studies during the past decade have provided a better understanding of the potential mechanisms responsible for the pathogenesis of preeclampsia. The initiating event in preeclampsia has been postulated to be reduced uteroplacental perfusion as a result of abnormal cytotrophoblast invasion of spiral arterioles. Placental ischemia/hypoxia is thought to lead to widespread activation/dysfunction of the maternal vascular endothelium which results in enhanced formation of endothelin, thromboxane, and superoxide, increased vascular sensitivity to angiotensin II, and decreased formation of vasodilators such as nitric oxide and prostacyclin. These endothelial abnormalities, in turn, cause hypertension by impairing renal function and increasing total peripheral resistance. While recent studies support a role for cytokines and other factors such as lipid peroxides and reactive oxygen intermediates as potential mediators of endothelial dysfunction, finding the link between placental ischemia/hypoxia and maternal endothelial and vascular abnormalities remains an important area of investigation. The quantitative importance of the various endothelial and humoral factors in mediating the vasoconstriction and elevation in arterial pressure during preeclampsia has also not been completely elucidated.

Blood Vessels↗
PubMed2002

Reduced endothelial NO-cGMP vascular relaxation pathway during TNF-alpha-induced hypertension in pregnant rats.

Placental ischemia during pregnancy is thought to release cytokines such as tumor necrosis factor-alpha (TNF-alpha), which may contribute to the increased vascular resistance associated with pregnancy-induced hypertension. We have reported that a chronic twofold elevation in plasma TNF-alpha increases blood pressure in pregnant but not in virgin rats; however, the vascular mechanisms are unclear. We tested the hypothesis that increasing plasma TNF-alpha during pregnancy impairs endothelium-dependent vascular relaxation and enhances vascular reactivity. Active stress was measured in aortic strips of virgin and late-pregnant Sprague-Dawley rats untreated or infused with TNF-alpha (200 ng x kg(-1) x day(-1) for 5 days) to increase plasma level twofold. Phenylephrine (Phe) increased active stress to a maximum of 4.2 +/- 0.4 x 10(3) and 9.9 +/- 0.7 x 10(3) N/m2 in control pregnant and TNF-alpha-infused pregnant rats, respectively. Removal of the endothelium enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. In endothelium-intact strips, ACh caused greater relaxation of Phe contraction in control than in TNF-alpha-infused pregnant rats. Basal and ACh-induced nitrite/nitrate production was less in TNF-alpha-infused than in control pregnant rats. Pretreatment of vascular strips with 100 microM N(G)-nitro-L-arginine methyl ester, to inhibit nitric oxide (NO) synthase, or 1 microM 1H-[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one, to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. Phe contraction and ACh relaxation were not significantly different between control and TNF-alpha-infused virgin rats. Thus an endothelium-dependent NO-cGMP-mediated vascular relaxation pathway is inhibited in late-pregnant rats infused with TNF-alpha. The results support a role for TNF-alpha as one possible mediator of the increased vascular resistance associated with pregnancy-induced hypertension.

Acetylcholine↗
PubMed2002

TNF-alpha enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats.

Tumor necrosis factor-alpha (TNF-alpha) is elevated in the plasma of preeclamptic women and may have a role in pregnancy-induced hypertension. However, whether the hemodynamic effects of TNF-alpha reflect the direct effects on vascular reactivity is unclear. We tested the hypothesis that TNF-alpha impairs endothelium-dependent relaxation and enhances vascular contraction in systemic vessels of pregnant rats. We measured isometric contraction in aortic strips isolated from virgin and pregnant Sprague-Dawley rats (nontreated vs. treated for 2 h with 10-1,000 pg/ml TNF-alpha). In endothelium-intact vascular strips, TNF-alpha caused greater enhancement of phenylephrine (Phe) contraction in pregnant than virgin rats. TNF-alpha caused significant inhibition of ACh- and bradykinin-induced vascular relaxation and nitrite/nitrate production that were more prominent in pregnant than virgin rats. N(G)-nitro-L-arginine methyl ester [L-NAME, 100 microM, an inhibitor of nitric oxide (NO) synthase] or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 1 microM, an inhibitor of cGMP production in smooth muscle) inhibited ACh relaxation and enhanced Phe contraction in nontreated but to a lesser extent in TNF-alpha-treated vessels, particularly those of pregnant rats. Endothelium removal enhanced Phe contraction in nontreated but not TNF-alpha-treated vessels, especially those of pregnant rats. Relaxation of Phe contraction with the NO donor sodium nitroprusside was not different between nontreated and TNF-alpha-treated vessels. Thus TNF-alpha enhances vascular contraction and inhibits endothelium-dependent NO-cGMP-mediated vascular relaxation in systemic vessels, particularly those of pregnant rats. The results support a direct role for TNF-alpha as a possible mediator of increased vascular resistance associated with pregnancy-induced hypertension.

Animals↗
PubMed2002

Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models.

Normal pregnancy is associated with reductions in total vascular resistance and arterial pressure possibly due to enhanced endothelium-dependent vascular relaxation and decreased vascular reactivity to vasoconstrictor agonists. These beneficial hemodynamic and vascular changes do not occur in women who develop preeclampsia; instead, severe increases in vascular resistance and arterial pressure are observed. Although preeclampsia represents a major cause of maternal and fetal morbidity and mortality, the vascular and cellular mechanisms underlying this disorder have not been clearly identified. Studies in hypertensive pregnant women and experimental animal models suggested that reduction in uteroplacental perfusion pressure and the ensuing placental ischemia/hypoxia during late pregnancy may trigger the release of placental factors that initiate a cascade of cellular and molecular events leading to endothelial and vascular smooth muscle cell dysfunction and thereby increased vascular resistance and arterial pressure. The reduction in uterine perfusion pressure and the ensuing placental ischemia are possibly caused by inadequate cytotrophoblast invasion of the uterine spiral arteries. Placental ischemia may promote the release of a variety of biologically active factors, including cytokines such as tumor necrosis factor-alpha and reactive oxygen species. Threshold increases in the plasma levels of placental factors may lead to endothelial cell dysfunction, alterations in the release of vasodilator substances such as nitric oxide (NO), prostacyclin (PGI(2)), and endothelium-derived hyperpolarizing factor, and thereby reductions of the NO-cGMP, PGI(2)-cAMP, and hyperpolarizing factor vascular relaxation pathways. The placental factors may also increase the release of or the vascular reactivity to endothelium-derived contracting factors such as endothelin, thromboxane, and ANG II. These contracting factors could increase intracellular Ca(2+) concentrations ([Ca(2+)](i)) and stimulate Ca(2+)-dependent contraction pathways in vascular smooth muscle. The contracting factors could also increase the activity of vascular protein kinases such as protein kinase C, leading to increased myofilament force sensitivity to [Ca(2+)](i) and enhancement of smooth muscle contraction. The decreased endothelium-dependent mechanisms of vascular relaxation and the enhanced mechanisms of vascular smooth muscle contraction represent plausible causes of the increased vascular resistance and arterial pressure associated with preeclampsia.

Animals↗
PubMed2002

Inducible nitric oxide synthase inhibition attenuates renal hemodynamics during pregnancy.

Acute, nonselective nitric oxide synthase inhibition in the pregnant rat decreases glomerular filtration rate and renal plasma flow, suggesting a role for nitric oxide in mediating renal vasodilation during pregnancy. As mid-gestation in the rat is associated with a significant increase in renal protein expression of inducible nitric oxide synthase, the aim of this study was to examine the role of inducible nitric oxide synthase in mediating renal hemodynamics changes at mid-gestation in the rat. At day 16 of pregnancy, glomerular filtration rate was significantly higher in pregnant rats compared with virgin rats (3.1 +/- 0.4 versus 2.7 +/- 0.3 mL/min, respectively; P<0.05), as was effective renal plasma flow (13.4 +/- 2.5 versus 10.9 +/- 2.2 mL/min, respectively; P<0.05). Acute administration of the inducible nitric oxide synthase selective inhibitor, AMT hydrochloride (750 nmol/h), markedly attenuated the increase in glomerular filtration rate observed in pregnant rats (2.3 +/- 0.2 mL/min, P<0.01 versus pregnant) without significantly altering glomerular filtration rate in virgin rats (2.1 +/- 0.2 mL/min). Acute AMT administration significantly decreased effective renal plasma flow in pregnant (8.9 +/- 1.8 mL/min, P<0.01 versus pregnant) and virgin rats (7.1 +/- 0.9 mL/min, P<0.05 versus virgin). Acute administration of EIT (380 nmol/h), another inducible nitric oxide synthase selective inhibitor, also attenuated pregnancy-induced increases in glomerular filtration rate (2.1 +/- 0.2, 2.8 +/- 0.3, and 2.3 +/- 0.3 mL/min; virgin, pregnant, and EIT, respectively) and effective renal plasma flow (8.5 +/- 1.1, 13.8 +/- 2.1, and 9.0 +/- 1.1 mL/min; virgin, pregnant, and EIT, respectively). Therefore, these findings suggest that inducible nitric oxide synthase may play an important role in mediating the renal hemodynamic changes that occur during normal pregnancy.

Animals↗
PubMed2002

Low-salt diet enhances vascular reactivity and Ca(2+) entry in pregnant rats with normal and reduced uterine perfusion pressure.

Salt moderation is often recommended to prevent excessive increases in blood pressure during pregnancy, particularly in women who are prone to pregnancy-induced hypertension; however, the vascular effects of low dietary salt intake during pregnancy are unclear. We investigated whether a low-salt diet during pregnancy alters the mechanisms of vascular smooth muscle contraction. Active stress and (45)Ca(2+) influx were measured in endothelium-denuded aortic strips of virgin and normal pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by reduction in uterine perfusion pressure (RUPP), fed either a normal-sodium (NS, 1% NaCl) or low-sodium diet (LS, 0.2% NaCl) for 7 days. The mean arterial pressure was as follows: virgin/NS 108 +/- 8, virgin/LS 117 +/- 7, pregnant/NS 102 +/- 3, pregnant/LS 117 +/- 4, RUPP/NS 119 +/- 3, and RUPP/LS 133 +/- 6 mm Hg. Phenylephrine (Phe) caused concentration-dependent increases in active stress and (45)Ca(2+) influx that were greater in RUPP rats than in normal pregnant or virgin rats and were enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. High KCl (16 to 96 mmol/L), which stimulates Ca(2+) entry from the extracellular space, also caused increases in active stress that were greater in RUPP than in normal pregnant, in pregnant/LS than in pregnant/NS, and in RUPP/LS than in RUPP/NS rats. The Phe-induced (45)Ca(2+) influx--active stress relation was greater in RUPP/NS than in pregnant/NS and was enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. In Ca(2+)-free (2 mmol/L ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetra-acetic acid) Krebs, stimulation of intracellular Ca(2+) release by Phe (10(-5) mol/L) or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. Thus, a low-salt diet in pregnant and RUPP rats is associated with increases in vascular reactivity that involves Ca(2+) entry from the extracellular space but not Ca(2+) release from the intracellular stores. The enhancement of the Phe-induced Ca(2+) influx--active stress relation in pregnant and RUPP rats on a low-salt diet suggests activation of other vascular contraction mechanisms in addition to Ca(2+) entry. Although it is difficult to extrapolate the experimental data in rats to clinical data in women, the increased vascular reactivity and Ca(2+) entry and the possible enhancement of additional vascular contraction mechanisms with a low-salt diet suggest that reduction of dietary salt intake should be carefully monitored during pregnancy and pregnancy-induced hypertension.

Animals↗