Protective effect of prenatal water restriction on offspring cardiovascular homeostasis in response to hemorrhage

2005 ◽  
Vol 288 (6) ◽  
pp. H2659-H2665 ◽  
Author(s):  
Mina Desai ◽  
Catalina Guerra ◽  
Shengbiao Wang ◽  
Michael G. Ross
Keyword(s):  
Blood Pressure ◽  
Protective Effect ◽  
Blood Volume ◽  
Plasma Osmolality ◽  
Systemic Hypertension ◽  
Plasma Sodium ◽  
Water Restriction ◽  
Arterial Blood ◽  
Ad Libitum ◽  
Cardiovascular Homeostasis

We determined the cardiovascular and AVP responses of prenatally dehydrated (PreDehy) neonates to intravascular hemorrhage. Ewes with singleton fetuses were subjected to water restriction from 110 days of gestation to full term to achieve hypernatremia of 8–10 meq/l. Water and food were provided ad libitum to control ewes. After delivery, water and food were provided ad libitum to ewes from both groups, and newborns were allowed to nurse ad libitum. At 15 ± 2 days of age, PreDehy and control lambs were prepared with bladder and femoral catheters and studied at 25 ± 2 days of age. After a 2-h basal period, lambs were hemorrhaged to 30% of blood volume over 1 h (0.5% of blood volume/min) and monitored 1 h after hemorrhage. Neonatal arterial blood pressure was measured, and blood samples were collected. Basal plasma sodium levels, plasma osmolality, hematocrit, and mean arterial pressure were increased in PreDehy lambs compared with controls. Both groups had similar basal AVP levels and heart rate. In response to hemorrhage, all parameters remained significantly elevated in PreDehy lambs. Blood pressure decreased less in PreDehy lambs than in controls. The hemorrhage-AVP threshold (percent blood volume withdrawal at which plasma AVP values significantly increased) was markedly elevated (20 vs. 15%) and peak hemorrhage-induced AVP plasma levels were lower (5.6 ± 1.5 vs. 10.1 ± 1.5 pg/ml, P < 0.01) in PreDehy lambs than in controls. Thus offspring of dehydrated ewes demonstrate enhanced AVP secretory responses to hypotension. Despite potential long-term adverse effects of systemic hypertension, these results suggest a protective effect of prenatal water restriction on offspring cardiovascular homeostasis during blood volume reduction.

Prenatal programming of hypernatremia and hypertension in neonatal lambs

2005 ◽  
Vol 288 (1) ◽  
pp. R97-R103 ◽  
Author(s):  
Michael G. Ross ◽  
Mina Desai ◽  
Catalina Guerra ◽  
Shengbiao Wang
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Plasma Osmolality ◽  
In Utero ◽  
Water Restriction ◽  
Arterial Blood ◽  
Basal Period ◽  
Ad Libitum ◽  
Hypotonic Saline ◽  
The Impact

Maternal water restriction and the accompanying dehydration-induced anorexia may induce long-term physiological changes in offspring. We determined the impact of prenatal hypertonicity (Pre-Dehy) on offspring cardiovascular and osmoregulatory function. Pre-Dehy lambs were exposed to in utero hypernatremia (8- to 10-meq increase; 110–150 days of gestation) induced by maternal water restriction. Control lambs were born to ewes provided ad libitum water and food throughout gestation. After delivery, all ewes were provided ad libitum water and all newborns were allowed ad libitum nursing. Lambs were prepared with vascular and bladder catheters at 15 ± 2 days of age and studied at 21 ± 2 days. After a 2-h basal period, lambs received an infusion of hypotonic (0.075 M) NaCl (0.15 ml·kg−1·h−1 iv) for 2 h. Lamb arterial blood pressure was monitored, and blood samples were obtained before, during, and after infusion. During the neonatal basal period, Pre-Dehy lambs had significantly increased plasma osmolality (302 ± 1 vs. 294 ± 1 mosmol/kgH2O, P < 0.01), sodium levels (144 ± 1 vs. 140 ± 1 meq/l, P < 0.01), hematocrit (28 ± 1% vs. 25 ± 1%, P < 0.05), and mean arterial blood pressure (79 ± 2 vs. 68 ± 1 mmHg, P < 0.001) compared with control lambs. Despite the infusion of hypotonic saline, Pre-Dehy lambs maintained relative hypertonicity, hypernatremia, and hypertension. However, plasma arginine vasopressin, glomerular filtration rate, and urinary osmolar and sodium excretion and clearance (per kg body wt) were similar in the groups. Offspring of prenatally water-restricted ewes exhibit hypernatremia, hypertonicity, and hypertension, which persist despite hypotonic saline infusion. In utero hypertonicity and perhaps maternal nutrient stress may program offspring osmoregulation and systemic arterial hypertension.

scholarly journals Programming of Hypertonicity in Neonatal Lambs: Resetting of the Threshold for Vasopressin Secretion

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4332-4337 ◽  
Author(s):  
Mina Desai ◽  
Catalina Guerra ◽  
Shengbiao Wang ◽  
Michael G. Ross
Keyword(s):  
Blood Pressure ◽  
Birth Weight ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Osmolality ◽  
In Utero ◽  
Plasma Sodium ◽  
Ad Libitum ◽  
Neonatal Lambs ◽  
And Control

Lambs exposed in utero to maternal hypertonicity demonstrate plasma hypertonicity and arterial hypertension. To determine whether hypertonicity is due to an altered osmoregulatory set point, we examined arginine-vasopressin and cardiovascular responses to hypertonic saline infusion in these offspring. Study lambs [dehydrated (Dehy)] were exposed to maternal hypernatremia (8–10 mEq/liter increase; 110–150 d gestation) induced by water restriction. Control singleton and Control twins were born to ewes provided ad libitum water. We anticipated reduced birth weight due to maternal dehydration-induced anorexia and therefore included a Control group of twin gestations to approach a similar birth weight near term. After delivery, ewes from all three groups were provided ad libitum water, and their newborns were allowed ad libitum nursing. At 15 ± 2 d of age, lambs were prepared with bladder and vascular catheters. At 23 ± 2 d, after a 2-h basal period, neonatal lambs were iv infused with hypertonic 0.83 m NaCl (0.075 ml/kg·h) for 2 h, followed by a 2-h recovery. Neonatal mean arterial pressure and urine flow were continuously monitored, and blood samples were obtained before, during, and after infusion. During the basal period, Dehy neonates and Control twins demonstrated significantly increased plasma sodium levels and mean arterial pressure than Control singletons. In addition, the Dehy neonates had significantly increased plasma osmolality compared with Control singletons and twins. In response to hypertonic infusion, the Dehy offspring continued to exhibit hypertonicity and hypertension. Importantly, plasma tonicity and blood pressure were greatest in Dehy singletons, lowest in singleton controls, and intermediate in twin controls. Furthermore, the plasma osmolality threshold for AVP secretion was significantly higher in Dehy singletons (290 ± 2 mOsm/kg) than Control twins (285 ± 1 mOsm/kg) and Control singletons (280 ± 2 mOsm/kg), indicating in utero programming of an altered set point for systemic osmolality and blood pressure regulation. Because both twin gestation and dehydration-anorexia incur potential fetal nutritional stress, the results suggest that both in utero hypertonicity and nutrition reduction contribute to offspring programming. We postulate that the nutritional stress associated with twins (as well as dehydration-induced anorexia) contributes to increased plasma sodium levels, whereas the increased plasma osmolality is due to in utero hypertonicity.

scholarly journals Early high-sodium solid diet does not affect sodium intake, sodium preference, blood volume and blood pressure in adult Wistar-Kyoto rats

2011 ◽  
Vol 106 (2) ◽  
pp. 292-296 ◽  
Author(s):  
Marcin Ufnal ◽  
Adrian Drapala ◽  
Mariusz Sikora ◽  
Tymoteusz Zera
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Blood Volume ◽  
Blood Level ◽  
Food Preference ◽  
Plasma Osmolality ◽  
Wky Rats ◽  
Arterial Blood ◽  
Significant Difference ◽  
Wistar Kyoto

A high-Na diet may lead to the development of hypertension in both humans and rats; however, the causes of Na intake in amounts greater than physiologically needed as well as the mechanisms whereby high-Na food elevates blood pressure are not clear. Therefore, we decided to test the hypothesis that a high-Na diet introduced after suckling affects Na intake, food preference, resting blood pressure and blood volume in adult rats. Male Wistar-Kyoto (WKY) rats, 4 weeks old, were divided into three groups and placed on either a high-Na (3·28%), a medium-Na (0·82%) or a regular diet (0·22%) with the same energy content for 8 weeks. Subsequently, food preference, resting arterial blood pressure, blood volume, plasma osmolality and Na blood level were evaluated. When offered a choice of diets, all the groups preferred the regular chow, and there was no significant difference in total Na intake between the groups. When the rats experienced the change from their initial chow to a new one with different Na content, they continued to eat the same amount of food. Body weight, resting arterial blood pressure, blood volume, plasma osmolality and Na blood level were comparable between the groups. In conclusion, the results show that a high-Na diet introduced immediately after suckling does not affect Na preference and Na intake in adult WKY rats. Furthermore, the findings provide evidence that both blood volume and arterial blood pressure are highly protected in normotensive rats on a high-Na diet.

Resonance in a mathematical model of baroreflex control: arterial blood pressure waves accompanying postural stress

2005 ◽  
Vol 288 (6) ◽  
pp. R1637-R1648 ◽  
Author(s):  
Peter E. Hammer ◽  
J. Philip Saul
Keyword(s):  
Blood Pressure ◽  
Mathematical Model ◽  
Blood Volume ◽  
Low Frequency ◽  
Pressure Waves ◽  
Central Blood Volume ◽  
Arterial Baroreflex ◽  
Arterial Blood ◽  
Gain Margin ◽  
The Stability

A mathematical model of the arterial baroreflex was developed and used to assess the stability of the reflex and its potential role in producing the low-frequency arterial blood pressure oscillations called Mayer waves that are commonly seen in humans and animals in response to decreased central blood volume. The model consists of an arrangement of discrete-time filters derived from published physiological studies, which is reduced to a numerical expression for the baroreflex open-loop frequency response. Model stability was assessed for two states: normal and decreased central blood volume. The state of decreased central blood volume was simulated by decreasing baroreflex parasympathetic heart rate gain and by increasing baroreflex sympathetic vaso/venomotor gains as occurs with the unloading of cardiopulmonary baroreceptors. For the normal state, the feedback system was stable by the Nyquist criterion (gain margin = 0.6), but in the hypovolemic state, the gain margin was small (0.07), and the closed-loop frequency response exhibited a sharp peak (gain of 11) at 0.07 Hz, the same frequency as that observed for arterial pressure fluctuations in a group of healthy standing subjects. These findings support the theory that stresses affecting central blood volume, including upright posture, can reduce the stability of the normally stable arterial baroreflex feedback, leading to resonance and low-frequency blood pressure waves.

Supine exercise restores arterial blood pressure and skin blood flow despite dehydration and hyperthermia

1999 ◽  
Vol 277 (2) ◽  
pp. H576-H583 ◽  
Author(s):  
José González-Alonso ◽  
Ricardo Mora-Rodríguez ◽  
Edward F. Coyle
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Arterial Blood Pressure ◽  
Blood Volume ◽  
Plasma Catecholamines ◽  
Central Blood Volume ◽  
Vascular Conductance ◽  
Arterial Blood ◽  
Cutaneous Vascular Conductance

We determined whether the deleterious effects of dehydration and hyperthermia on cardiovascular function during upright exercise were attenuated by elevating central blood volume with supine exercise. Seven trained men [maximal oxygen consumption (V˙o 2 max) 4.7 ± 0.4 l/min (mean ± SE)] cycled for 30 min in the heat (35°C) in the upright and in the supine positions (V˙o 2 2.93 ± 0.27 l/min) while maintaining euhydration by fluid ingestion or while being dehydrated by 5% of body weight after 2 h of upright exercise. When subjects were euhydrated, esophageal temperature (Tes) was 37.8–38.0°C in both body postures. Dehydration caused equal hyperthermia during both upright and supine exercise (Tes = 38.7–38.8°C). During upright exercise, dehydration lowered stroke volume (SV), cardiac output, mean arterial pressure (MAP), and cutaneous vascular conductance and increased heart rate and plasma catecholamines [30 ± 6 ml, 3.0 ± 0.7 l/min, 6 ± 2 mmHg, 22 ± 8%, 14 ± 2 beats/min, and 50–96%, respectively; all P < 0.05]. In contrast, during supine exercise, dehydration did not cause significant alterations in MAP, cutaneous vascular conductance, or plasma catecholamines. Furthermore, supine versus upright exercise attenuated the increases in heart rate (7 ± 2 vs. 9 ± 1%) and the reductions in SV (13 ± 4 vs. 21 ± 3%) and cardiac output (8 ± 3 vs. 14 ± 3%) (all P< 0.05). These results suggest that the decline in cutaneous vascular conductance and the increase in plasma norepinephrine concentration, independent of hyperthermia, are associated with a reduction in central blood volume and a lower arterial blood pressure.

Intraruminal rehydration of ovine fetuses

1991 ◽  
Vol 261 (6) ◽  
pp. R1381-R1387
Author(s):  
M. G. Ross ◽  
D. J. Sherman ◽  
M. G. Ervin ◽  
L. Day
Keyword(s):  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Filtration Rate ◽  
Plasma Osmolality ◽  
Urine Osmolality ◽  
Distilled Water ◽  
Intravascular Volume ◽  
Fetal Plasma ◽  
Arterial Blood ◽  
Arterial Po2

During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.

Estimation of blood pressure-related parameters by electrical impedance measurement

1992 ◽  
Vol 73 (5) ◽  
pp. 1946-1957 ◽  
Author(s):  
J. H. Muntinga ◽  
K. R. Visser
Keyword(s):  
Blood Pressure ◽  
Blood Volume ◽  
Electrical Impedance ◽  
Cuff Pressure ◽  
Arterial Compliance ◽  
Blood Pressure Measurement ◽  
Venous Blood ◽  
Impedance Measurement ◽  
Total Blood ◽  
Arterial Blood

In 13 healthy volunteers a computerized experimental set-up was used to measure the electrical impedance of the upper arm at changing cuff pressure, together with the finger arterial blood pressure in the contralateral arm. On the basis of a model for the admittance response, the arterial blood volume per centimeter length (1.4 +/- 0.3 ml/cm), the venous blood volume as a percentage of the total blood compartment (49.2 +/- 12.6%), and the total arterial compliance as a function of mean arterial transmural pressure were estimated. The effective physiological arterial compliance amounted to 2.0 +/- 1.3 microliters.mmHg-1.cm-1 and the maximum compliance to 33.4 +/- 12.0 microliters.mmHg-1.cm-1. Additionally, the extravascular fluid volume expelled by the occluding cuff (0.3 +/- 0.3 ml/cm) was estimated. These quantities are closely related to patient-dependent sources of an unreliable blood pressure measurement and vary with changes in cardiovascular function, such as those found in hypertension. Traditionally, a combination of several methods is needed to estimate them. Such methods, however, usually neglect the contribution of extravascular factors.

Coevolution of the rennin–angiotensin system and the nervous control of blood circulation

1984 ◽  
Vol 62 (2) ◽  
pp. 137-147 ◽  
Author(s):  
John X. Wilson
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Blood Volume ◽  
Vascular Resistance ◽  
Renin Angiotensin System ◽  
Peripheral Vascular Resistance ◽  
Peripheral Vascular ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood

The mammalian renin–angiotensin system appears to be involved in the maintenance of blood volume and pressure because (i) sodium depletion, hypovolemia, and hypotension increase renin levels, and (ii) administration of exogenous angiotensin II rapidly increases mineralocorticoid and antidiuretic hormone production, transepithelial ion transport, drinking behavior, and peripheral vascular resistance. Are these also the physiological properties of the renin–angiotensin system in nonmammalian species? Signals for altered levels of renin activity have yet to be conclusively identified in nonmammalian vertebrates, but circulating renin levels are elevated by hypotension in teleost fish and birds. Systemic injection of angiotensin II causes an increase in arterial blood pressure in all the vertebrates studied, suggesting that barostatic control is a universal function of this hormone. Angiotensin II alters vascular tone by direct action on arteriolar muscles in some species, but at concentrations of the hormone which probably are unphysiological. More generally, angiotensin II increases blood pressure indirectly, by acting on the sympathetic nervous system. Catecholamines, derived from chromaffin cells and (or) from peripheral adrenergic nerves, mediate some portion of the vasopressor response to angiotensin II in cyclostomes, elasmobranchs, teleosts, amphibians, reptiles, mammals, and birds. Alteration of sympathetic outflow is a prevalent mechanism through which the renin–angiotensin system may integrate blood volume, cardiac output, and peripheral vascular resistance to achieve control of blood pressure and adequate perfusion of tissues.

P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Keck ◽  
H De Almeida ◽  
D Compere ◽  
N Inguimbert ◽  
A Flahault ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
Sulfonic Acid ◽  
Plasma Sodium ◽  
High Dose ◽  
Hypertensive Rats ◽  
Arterial Blood ◽  
Angiotensin Iii ◽  
Aminopeptidase A ◽  
Orally Active

Abstract Background Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration. Purpose However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity. Methods We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements. Results We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p<0.001), sustained over ten hours (−21±12 mmHg, p<0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. Conclusions This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment. Acknowledgement/Funding ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.

Osmotic regulation of vasopressin in the cat

1981 ◽  
Vol 240 (2) ◽  
pp. E108-E111
Author(s):  
T. A. Reaves ◽  
H. M. Liu ◽  
M. M. Qasim ◽  
J. N. Hayward
Keyword(s):  
Regression Analysis ◽  
Arginine Vasopressin ◽  
Regression Line ◽  
Plasma Osmolality ◽  
Fluid Restriction ◽  
Base Line ◽  
Osmotic Regulation ◽  
Arterial Blood Supply ◽  
Arterial Blood ◽  
Ad Libitum

This study examines the effects of blood osmolality on the release of arginine vasopressin (AVP) in the cat. Prior to the beginning of the experiments, the chamber-isolated, unanesthetized cat, allowed water ad libitum had a constant plasma osmolality averaging 320 +/- 2 (SE) mosmol/kg and a constant plasma AVP averaging 3.4 +/- 0.7 microU/ml. Water loading decreased plasma osmolality to 312 +/- 2 mosmol/kg and lowered plasma AVP to 1.3 +/- 0.2 microU/ml. As dehydration occurred during fluid restriction, the plasma osmolality increased and plasma AVP rose to 8 times the base line after 2 days. The rise in plasma AVP correlated linearly with the rise in plasma osmolality (r = 0.81; P less than 0.01). The cat's osmotic-vasopressin relationships are unique among mammals, revealing an elevated osmotic "set point" (threshold) and with regression analysis an increased "gain" or "'sensitivity" (increased slope of the regression line). We speculate that these unusual osmotic-AVP relationships may be related to some specialized features of the cat, such as hypothalamic anatomy or cerebral arterial blood supply.

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