Intrauterine L-NAME Exposure Weakens the Development of Sympathetic Innervation and Induces the Remodeling of Arterial Vessels in Two-Week-Old Rats

Nitric oxide (NO) has been shown to stimulate differentiation and increase the survival of ganglionic sympathetic neurons. The proportion of neuronal NOS-immunoreactive sympathetic preganglionic neurons is particularly high in newborn rats and decreases with maturation. However, the role of NO in the development of vascular sympathetic innervation has never been studied before. We tested the hypothesis that intrauterine NO deficiency weakened the development of vascular sympathetic innervation and thereby changed the contractility of peripheral arteries and blood pressure level in two-week-old offspring. Pregnant rats consumed NOS inhibitor L-NAME (250 mg/L in drinking water) from gestational day 10 until delivery. Pups in the L-NAME group had a reduced body weight and blood level of NO metabolites at 1–2 postnatal days. Saphenous arteries from two-week-old L-NAME offspring demonstrated a lower density of sympathetic innervation, a smaller inner diameter, reduced maximal active force and decreased α-actin/β-actin mRNA expression ratio compared to the controls. Importantly, pups in the L-NAME group exhibited decreased blood pressure levels before, but not after, ganglionic blockade with chlorisondamine. In conclusion, intrauterine L-NAME exposure is followed by the impaired development of the sympathetic nervous system in early postnatal life, which is accompanied by the structural and functional remodeling of arterial blood vessels.

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Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00783.2007 ◽

2008 ◽

Vol 295 (5) ◽

pp. R1546-R1554 ◽

Cited By ~ 8

Author(s):

Melissa Li ◽

Xiaoling Dai ◽

Stephanie Watts ◽

David Kreulen ◽

Gregory Fink

Keyword(s):

Blood Pressure ◽

Sympathetic Innervation ◽

Sympathetic Ganglia ◽

Plasma Norepinephrine ◽

Sprague Dawley ◽

Surgical Ablation ◽

Arterial Blood ◽

Sprague Dawley Rats ◽

Induced Hypertension ◽

Hypertension Development

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.

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Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00090.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. R1657-R1665 ◽

Cited By ~ 4

Author(s):

Annie Beauséjour ◽

Véronique Houde ◽

Karine Bibeau ◽

Rébecca Gaudet ◽

Jean St-Louis ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Nitrosative Stress ◽

Gestational Hypertension ◽

Sodium Intake ◽

Pregnant Rats ◽

High Sodium ◽

High Sodium Intake ◽

Arterial Blood ◽

Cardiac Ventricle

Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F2α (8-iso-PGF2α) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na+-K+-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-α)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na+-K+-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF2α, and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension.

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Decrease in heart rates by artificial CO2 hot spring bathing is inhibited by β1-adrenoceptor blockade in anesthetized rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00812.2003 ◽

2004 ◽

Vol 96 (1) ◽

pp. 226-232 ◽

Cited By ~ 18

Author(s):

Masaaki Hashimoto ◽

Noriyuki Yamamoto

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Skin Color ◽

Hot Spring ◽

Tap Water ◽

Sympathetic Innervation ◽

Tissue Blood Flow ◽

Cardiac Sympathetic Innervation ◽

Human Foot ◽

Arterial Blood

To investigate the effects of carbon dioxide (CO2) hot spring baths on physiological functions, head-out immersion of urethane-anesthetized, fursheared male Wistar rats was performed. Animals were immersed in water (30 or 35°C) with high-CO2 content (∼1,000 parts/million; CO2-water). CO2-water for bathing was made by using an artificial spa maker with normal tap water and high-pressure CO2 from a gas cylinder. When a human foot was immersed for 10 min in the CO2-water at 35°C, the immersed skin reddened, whereas skin color did not change in normal tap water at the same temperature. Arterial blood pressure, heart rate (HR), underwater skin tissue blood flow, and temperatures of the colon and immersed skin were continuously measured while animals were immersed in a bathtub of water for ∼30 min at room temperature (26°C). Immersed skin vascular resistance, computed from blood pressure and tissue blood flow, was significantly lower in the CO2-water bath than in tap water at 30°C, but no differences were apparent at 35°C. HR of rats in CO2-water was significantly slower than in tap water at 35°C. Decreased HR in CO2-water was inhibited by infusion of atenolol (β1-adrenoceptor blocker), but it was unaffected by atropine (muscarinic cholinoceptor blocker). Theses results suggest that bradycardia in CO2 hot spring bathing is caused by inhibition of the cardiac sympathetic innervation. This CO2-water maker should prove a useful device for acquiring physiological evidence of balneotherapy.

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Magnesium Lithospermate B Downregulates the Levels of Blood Pressure, Inflammation, and Oxidative Stress in Pregnant Rats with Hypertension

International Journal of Hypertension ◽

10.1155/2020/6250425 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Kaixiang Xu ◽

Xiaohong Zang ◽

Mian Peng ◽

Qian Zhao ◽

Binbin Lin

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Gestational Hypertension ◽

Protective Effects ◽

Urine Protein ◽

Pregnant Rats ◽

Protein Levels ◽

Arterial Blood ◽

Magnesium Lithospermate B ◽

And Oxidative Stress

Background. Magnesium lithospermate B (MLB) was shown to suppress oxidative stress and reduce hypertension, but the role of MLB in pregnancy-induced hypertension (PIH) remains unknown. The objective of this study was to demonstrate the effects of MLB on rats with PIH. Methods. A total of 40 pregnant SD rats were selected, and 30 rats were orally given NG-nitro-L-arginine methyl ester (L-NAME, 60 mg/kg/day) to establish PIH rat models. Rats were equally divided into four groups: control, PIH, 5 mg/kg MLB, and 10 mg/kg MLB. MLB was consecutively administered into PIH rats for one week. The effects of MLB on mean arterial blood pressure (MAP), urine protein level, inflammation, and oxidative stress together with angiogenesis were analyzed. Results. MLB prevented the elevation in MAP and urine protein levels induced by L-NAME. The activities of inflammatory cytokines were highly increased in serum and placental tissues of PIH rats, while cotreatment with MLB partially reversed the activities of these cytokines. MLB also recovered the expression of reactive oxygen species (ROS) in plasma of PIH rats together with levels of oxidative stress and antioxidant capacity in the placenta of PIH rats. The decreased expressions of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and NO observed in PIH rats were increased by MLB. In addition, 10 mg/kg MLB exhibited higher protective effects as compared to lower doses of 5 mg/kg. Conclusion. This study demonstrated that pretreatment with MLB decreased MAP, inflammation, and oxidative stress in rats with gestational hypertension.

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Abstract 273: Increased Blood Pressure and Proteinuria and Absence of Increased Nitric Oxide (NO) Production During Pregnancy in the Dahl Salt Sensitive (S) Rat

Hypertension ◽

10.1161/hyp.62.suppl_1.a273 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Ellen E Gillis ◽

Jennifer N Mooney ◽

Jan M Williams ◽

Michael R Garrett ◽

Jennifer M Sasser

Keyword(s):

Blood Pressure ◽

Genetic Model ◽

Late Pregnancy ◽

Normal Pregnancy ◽

Kidney Cortex ◽

No Production ◽

Pregnant Rats ◽

Telemetry Unit ◽

Nos Inhibitor ◽

Volume Retention

In normal pregnancy, systemic vasodilation due to increased NO production allows a drop in blood pressure (BP) despite increased volume retention. Little is known about the pathogenesis of preeclampsia, defined by increased BP and proteinuria, due to a lack of animal models that spontaneously develop the disease. Here we tested the hypothesis that the Dahl S rat, a genetic model of hypertension and kidney disease, is also a spontaneous model of preeclampsia. Female Dahl S rats were implanted with a telemetry unit, and baseline BP was recorded. Rats were placed in metabolic cages for 24 hr urine collection while on a low nitrate diet, and urinary protein and NO metabolite concentrations were measured via Bradford and Greiss assays, respectively. There were no differences in baseline BP (152±1 vs 151±4 mmHg) or proteinuria (61±10 vs 60±17 mg/d) in the rats selected for mating vs virgin rats (n=5-7). Pregnancy was confirmed by presence of sperm (day 1). Measurements were made during mid and late pregnancy (days 10-11, 17-18), and terminal measurements were taken on day 19. Pregnant rats exhibited an increase in BP and proteinuria with no change in urinary NOx excretion (Table), while no changes were observed in age-matched virgin rats. Kidney cortex abundance of neither NOS1 nor NOS3 was increased at late pregnancy; however, plasma concentration of the endogenous NOS inhibitor ADMA was increased in late pregnant compared to virgin rats (0.82±0.06 vs. 0.62±0.06 μM, p<0.05). These data suggest that the Dahl S rat cannot upregulate NO production during pregnancy; therefore, this relative NO deficiency may contribute to worsening hypertension and proteinuria during pregnancy in this strain.

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Neuronal NO promotes cerebral cortical hyperemia during cortical spreading depression in rabbits

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.3.h1315 ◽

1997 ◽

Vol 272 (3) ◽

pp. H1315-H1322 ◽

Cited By ~ 4

Author(s):

D. M. Colonna ◽

W. Meng ◽

D. D. Deal ◽

M. Gowda ◽

D. W. Busija

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Mean Arterial Blood Pressure ◽

Repeated Measures ◽

Cortical Spreading Depression ◽

Spreading Depression ◽

Cerebrovascular Resistance ◽

Arterial Blood ◽

Repeated Measures Analysis ◽

Nos Inhibitor

Temporary elevations in cortical cerebral blood flow (CBF) accompany cortical spreading depression (CSD) in anesthetized animals. We tested the hypothesis that nitric oxide (NO) is an important promotor of CSD-induced cortical hyperemia in urethan-anesthetized rabbits. CBF was measured at four time points by administration of 15-microm microspheres with the reference withdrawal technique. Intravenous administration of the nonspecific NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine increased mean arterial blood pressure and resting cerebrovascular resistance and attenuated CSD-induced hyperemia. Cortical CBF before intraperitoneal 7-nitroindazole (7-NI), a neuronal NOS inhibitor, was 42 +/- 8 and 124 +/- 19 ml x 100 g(-1) x min(-1) at baseline and during CSD, respectively (P < 0.05 by repeated-measures analysis of variance). After 7-NI administration, mean arterial blood pressure, CBF, and cerebrovascular resistance were unchanged from baseline values; cortical CBF was 38 +/- 4 and 90 +/- 8 ml x 100 g(-1) x min(-1) post-7-NI at rest and during a second CSD, respectively. Similar to N(omega)-nitro-L-arginine, 7-NI decreased the cortical hyperemic response during CSD (P < 0.05 by repeated-measures analysis of variance). We conclude that neuronal NOS promotes the temporary cortical hyperemia observed during CSD.

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Muscle–Nerve Sympathetic Activity in Man. Relationship to Blood Pressure in Resting Normo- and Hyper-Tensive Subjects

Clinical Science ◽

10.1042/cs055387s ◽

1978 ◽

Vol 55 (s4) ◽

pp. 387s-389s ◽

Cited By ~ 1

Author(s):

G. Sundlöf ◽

B. G. Wallin

Keyword(s):

Blood Pressure ◽

Negative Correlation ◽

Sympathetic Activity ◽

Diastolic Pressure ◽

Pressure Fluctuations ◽

Blood Pressure Level ◽

Heart Beat ◽

Arterial Blood ◽

Muscle Nerve ◽

Pressure Changes

1. Simultaneous recordings of multi-unit muscle nerve sympathetic activity and arterial blood pressure were made in 29 subjects, 17 healthy and 12 hypertensive. The neural activity, quantified by counting the number of pulse-synchronous sympathetic bursts in the mean voltage neurogram (burst incidence), was plotted against blood pressure. The effect of spontaneous temporary blood pressure fluctuations was studied by correlating different pressure parameters of individual heart beats to the occurrence of a sympathetic burst. 2. Between subjects there were marked differences in burst incidence but no correlation was found to interindividual differences in blood pressure level. 3. When for each heart beat the occurrence of a burst was correlated to different pressure parameters there was a close negative correlation to diastolic, a low correlation to systolic, and an intermediate negative correlation to mean blood pressure. 4. In a given subject, when comparing heart beats with the same diastolic pressure, the occurrence and the amplitudes of the sympathetic bursts were higher during falling than during rising pressure. This directional dependence of the muscle—nerve sympathetic activity was slightly more pronounced in the hypertensive group, but this was considered secondary to the hypertension. 5. The findings of an intimate correlation with dynamic variations in blood pressure and the absence of correlation to the static blood pressure suggest that the sympathetic outflow to skeletal muscle is of importance for buffering acute blood pressure changes but has little influence on the long-term blood pressure.

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Paradoxical hypotension following increased hematocrit and blood viscosity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00490.2005 ◽

2005 ◽

Vol 289 (5) ◽

pp. H2136-H2143 ◽

Cited By ~ 63

Author(s):

Judith Martini ◽

Benoît Carpentier ◽

Adolfo Chávez Negrete ◽

John A. Frangos ◽

Marcos Intaglietta

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Blood Viscosity ◽

Exchange Transfusion ◽

Vessel Diameter ◽

No Production ◽

Packed Red Blood Cells ◽

Arterial Blood ◽

Nos Inhibitor ◽

Window Chamber

Hematocrit (Hct) of awake hamsters and CD-1 mice was acutely increased by isovolemic exchange transfusion of packed red blood cells (RBCs) to assess the relation between Hct and blood pressure. Increasing Hct 7–13% of baseline decreased mean arterial blood pressure (MAP) by 13 mmHg. Increasing Hct above 19% reversed this trend and caused MAP to rise above baseline. This relationship is described by a parabolic function ( R2 = 0.57 and P < 0.05). Hamsters pretreated with the nitric oxide (NO) synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) and endothelial NOS-deficient mice showed no change in MAP when Hct was increased by <19%. Nitrate/nitrite plasma levels of Hct-augmented hamsters increased relative to control and l-NAME treated animals. The blood pressure effect was stable 2 h after exchange transfusion. These findings suggest that increasing Hct increases blood viscosity, shear stress, and NO production, leading to vasodilation and mild hypotension. This was corroborated by measuring A1 arteriolar diameters (55.0 ± 21.5 μm) and blood flow in the hamster window chamber preparation, which showed statistically significant increased vessel diameter (1.04 ± 0.1 relative to baseline) and microcirculatory blood flow (1.39 ± 0.68 relative to baseline) after exchange transfusion with packed RBCs. Larger increases of Hct (>19% of baseline) led blood viscosity to increase >50%, overwhelming the NO effect through a significant viscosity-dependent increase in vascular resistance, causing MAP to rise above baseline values.

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Plasma Noradrenaline and the Pressor Action of Exogenous Noradrenaline in Normotensive Subjects and Patients with Essential Hypertension

Clinical Science ◽

10.1042/cs055061s ◽

1978 ◽

Vol 55 (s4) ◽

pp. 61s-63s ◽

Cited By ~ 1

Author(s):

T. Philipp ◽

A. Distler ◽

U. Cordes ◽

H. P. Wolff

Keyword(s):

Blood Pressure ◽

Essential Hypertension ◽

Arterial Blood Pressure ◽

Inverse Relationship ◽

Pressor Response ◽

Blood Pressure Level ◽

Plasma Noradrenaline ◽

Arterial Blood ◽

Adrenergic Activity ◽

Normotensive Subjects

1. An inverse relationship was found between plasma noradrenaline and reactivity to exogenous noradrenaline in normotensive subjects. 2. The relationship between plasma noradrenaline and reactivity was disturbed in age-matched patients with essential hypertension. 3. A multiple-regression analysis showed a highly significant correlation between adrenergic activity and reactivity to noradrenaline and the mean arterial blood pressure level (r = 0·91). The results suggest that adrenergic activity and pressor response to noradrenaline combined are important determinants of arterial blood pressure. 4. An inverse relationship could also be demonstrated between plasma renin activity and reactivity to exogenous angiotensin II. No difference was observed between normotensive and hypertensive subjects.

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Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00689.2011 ◽

2012 ◽

Vol 303 (5) ◽

pp. R527-R538 ◽

Cited By ~ 4

Author(s):

Ruslan Tiniakov ◽

Kalipada Pahan ◽

Karie E. Scrogin

Keyword(s):

Blood Pressure ◽

Hemorrhagic Shock ◽

Arterial Blood Pressure ◽

Sympathetic Innervation ◽

Hypovolemic Shock ◽

Pressor Effect ◽

Venous Tone ◽

Blood Withdrawal ◽

Arterial Blood ◽

Splanchnic Nerves

Administration of the 5-HT1A receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla.

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