Blood Pressure In Adult Rats Research Articles

Salt Overload During Postnatal Period Promotes Neurogenic‐mediated Increase of Arterial Blood Pressure in Adult Rats

The present study evaluated the effects of salt (NaCl) overload during the postnatal phases on cardiovascular parameters, cardiac function and cardiovascular responses induced by MnPO blockade in adulthood. 21 days‐old male Wistar rats were maintained on 0.3 M NaCl solution and food for 60 days (experimental group; EG); the control group was maintained on tap water and food. Later, both groups were maintained on tap water and food for 15 days (recovery). After the recovery period, baseline mean arterial pressure (MAP) and heart rate (HR) were recorded in unanaesthetized rats. The EG presented increased MAP (118.3 ± 2.7 mmHg vs. 98.6 ± 2.6 mmHg) and HR (398.2 ± 7.5 bpm vs. 365.4 ± 12.2 bpm) when compared to control group. To evaluate the cardiac function, the isolated hearts were perfused using the Langendorff technique in constant flow; after the basal recording, the hearts were submitted to ischemia/reperfusion. The salt overload did not affect the cardiac function in basal conditions. However, during the reperfusion, the hearts from EG presented increased intraventricular diastolic pressure (20.5 ± 5.16 mmHg vs. 11.5 ± 1.6 mmHg) and increased duration of reperfusion arrhythmias (208.8 ± 32.9 s vs. 75.0 ± 7.8 s), when compared to control group. Muscimol nanoinjections into MnPO promoted a decrease of MAP in both control and experimental rats, however, the decrease was greater in the EG (‐23.68 ± 1.46 mmHg vs. ‐15.58 ± 1.57 mmHg). These results demonstrate that postnatal salt overload alters cardiovascular regulation in adulthood. However, other studies are required to clarify the mechanisms by which the changes occur.Sponsors: Fapeg, Capes, CnPq

High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats.

Epigenetic studies suggest that diseases that develop in adulthood are related to certain conditions to which the individual is exposed during the initial stages of life. Experimental evidence has demonstrated that offspring born to mothers maintained on high-Na diets during pregnancy have higher mean arterial pressure (MAP) in adulthood. Although these studies have demonstrated the importance of prenatal phases to hypertension development, no evidence regarding the role of high Na intake during postnatal phases in the development of this pathology has been reported. Therefore, in the present study, the effects of Na overload during childhood on induced water and Na intakes and on cardiovascular parameters in adulthood were evaluated. Experiments were carried out in two groups of 21-d-old rats: experimental group, maintained on hypertonic saline (0.3 m-NaCl) solution and food for 60 d, and control group, maintained on tap water and food. Later, both groups were given water and food for 15 d (recovery period). After the recovery period, chronic cannulation of the right femoral artery was performed in unanaesthetised rats to record baseline MAP and heart rate (HR). The experimental group was found to have increased basal MAP (98.6 (sem 2.6) v. 118.3 (sem 2.7) mmHg, P< 0.05) and HR (365.4 (sem 12.2) v. 398.2 (sem 7.5) beats per min, P< 0.05). There was a decrease in the baroreflex index in the experimental group when compared with that in the control group. A water and Na intake test was performed using furosemide. Na depletion was found to induce an increase in Na intake in both the control and experimental groups (12.1 (sem 0.6) ml and 7.8 (sem 1.1), respectively, P< 0.05); however, this increase was of lower magnitude in the experimental group. These results demonstrate that postnatal Na overload alters behavioural and cardiovascular regulation in adulthood.

Abstract 403: Renal Denervation Reveals Renal Sympathetic Activation in Adult Rats Exposed to Early Life Stress

We previously reported that maternal separation (MS), a model of early life stress, does not modify baseline blood pressure in adult rats, but increases sensitivity to hypertensive stimuli. Under baseline conditions, adult male rats exposed to MS have significantly reduced glomerular filtration rate (GFR). Acute phenylephrine-induced reductions in renal blood flow is significantly attenuated in rats exposed to MS compared to control rats. Furthermore, norephinephrine (NE) content was increased in renal cortex of MS rats compared to control rats (p&lt;0.05). These data indicate that MS induces increased renal sympathetic outflow. Thus, we hypothesized that renal denervation will normalize GFR in rats exposed to MS. Male WKY rat pups were separated from their mothers for 3 hrs/day during the morning hours from day 2 to 14 of life. Male non-separated littermates served as control rats. Experiments were performed in 300-320 g adult rats. Denervation (DnX) was performed mechanically stripping all visible renal nerves followed by topical phenol (10%) on the renal artery. Control-sham, MS-sham, control-DnX, and MS-DnX rats were instrumented with catheters in the femoral vein and abdominal aorta. Rats were placed in metabolic cages, connected to swivels, and allowed to recover for 4-5 days. Sodium intake was clamped at 2.8 mEq/day in both groups by combining sodium deficient diet and 24 hr/day 0.9% iv saline infusion (20 ml/day). GFR was determined by plasma clearance of [125I]iothalamate in the conscious state. During baseline conditions, MAP was not different between control-sham and MS-sham rats (99±4 vs 97±2 mmHg, respectively). MAP was reduced in both control-DnX and MS-DnX rats (91±2 mmHg and 83±3 mmHg, p&lt;0.05, respectively) compared with the respective sham group. The reduction in MAP tended to be greater in MS than in control rats (-9±1 and -14±2 mmHg, p=0.074). DnX did not modify GFR in control rats (sham: 3.1±0.1 ml/min vs DnX: 3.5±0.4 ml/min). However, DnX significantly increased GFR in rats exposed to MS (sham: 2.4±0.2 ml/min vs DnX: 3.8±0.4 ml/min, p&lt;0.05). These data support our hypothesis that MS induces increased renal sympathetic tone to reduce GFR in MS male rats, and may contribute to the exacerbated response to hypertensive stimuli observed in MS rats.

Preventive dietary potassium supplementation in young salt-sensitive Dahl rats attenuates development of salt hypertension by decreasing sympathetic vasoconstriction

Increased potassium intake attenuates the development of salt-dependent hypertension, but the detailed mechanisms of blood pressure (BP) reduction are still unclear. The aims of our study were (i) to elucidate these mechanisms, (ii) to compare preventive potassium effects in immature and adult animals and (iii) to evaluate the therapeutic effects of dietary potassium supplementation in rats with established salt hypertension. Young (4-week-old) and adult (24-week-old) female salt-sensitive Dahl rats were fed a high-salt diet (5% NaCl) or a high-salt diet supplemented with 3% KCl for 5 weeks. The participation of vasoconstrictor (renin-angiotensin and sympathetic nervous systems) and vasodilator systems [prostanoids, Ca(2+) -activated K(+) channels, nitric oxide (NO)] was evaluated using a sequential blockade of these systems. Preventive potassium supplementation attenuated the development of severe salt hypertension in young rats, whereas it had no effects on BP in adult rats with moderate hypertension. Enhanced sympathetic vasoconstriction was responsible for salt hypertension in young rats and its attenuation for potassium-induced BP reduction. Conversely, neither salt hypertension nor its potassium-induced attenuation were associated with significant changes of the vasodilator systems studied. The relative deficiency of vasodilator action of NO and Ca(2+) -activated K(+) channels in salt hypertensive Dahl rats was not improved by potassium supplementation. The attenuation of enhanced sympathetic vasoconstriction is the principal mechanism of antihypertensive action exerted by preventive potassium supplementation in immature Dahl rats. Dietary potassium supplementation has no preventive effects on BP in adult salt-loaded animals or no therapeutic effects on established salt hypertension in young rats.

Cardiac activity and blood pressure in rats during selective blockade of various subtypes of muscarinic cholinoceptors

Cardiac activity and blood pressure in adult rats were recorded during selective blockade of cholinoceptors. Blockade of muscarinic M1 and M2-cholinoceptors had little effect on cardiac activity. Blockade of muscarinic M3-cholinoceptors was followed by heart acceleration. The data suggest that the tonic inhibitory influence of the vagus nerve is mediated via cardiac muscarinic M3-cholinoceptors. Electrostimulation of the right vagus nerve during selective blockade of various subtypes of muscarinic cholinoceptors was followed by the decrease in heart rate. Our results indicate that muscarinic cholinoceptors play a role in the immediate inhibition of cardiac activity upon vagus nerve stimulation.

Central and peripheral contributions to obesity‐associated hypertension: impact of early overnourishment

Obesity induced by a high-fat diet was associated with increased tail-cuff blood pressure in adult rats. The mechanisms underlying obesity-related hypertension are unclear, but increased sympathetic activation most probably plays a role. Neuroendocrine alterations observed in obesity may influence both feeding patterns and blood pressure. Work from our laboratory has shown that chronic overfeeding in rats leads to changes in neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alphaMSH) in the hypothalamus. These peptides have central effects on blood pressure, indicating that obesity-related changes in the CNS may impact on cardiovascular function. Population studies suggest that nutrition in early life can influence the subsequent risk of obesity and high blood pressure. To examine the impact of early postnatal overnutrition on blood pressure and adipose-derived mediators, we adjusted rat litters to 3 or 12 pups (overnutrition and control, respectively). Pups raised in small litters were 15% heavier at weaning, and this intervention was associated with a modest elevation of blood pressure and body weight as adults (16 weeks). Animals raised in small litters had increased 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mRNA in white adipose tissue as adults, which may impact on cardiovascular function. Adjustment of diet after weaning, to 30% fat diet or standard chow, allowed comparison of the impact of different periods of overnourishment. Implementation of a high-fat diet at weaning overcame the effect of litter size on body weight from 10 weeks of age. Blood pressure rose progressively with high-fat feeding and was positively correlated with leptin and body weight. Chronic consumption of a high-fat diet led to marked increases in leptin and insulin and modest increases in blood pressure, and impacts on brain transmitters implicated in the regulation of both appetite and blood pressure. Overnourishment during early postnatal development led to profound changes in body weight at weaning, which tended to abate with maturation. It also led to long-term changes in some adipose-derived mediators, possibly increasing cardiovascular risk.

Prenatal Dietary Docosahexaenoic Acid Supplementation in Combination with Protein Restriction Does Not Affect Blood Pressure in Adult Wistar Rats

Recent findings indicate that prenatal protein restriction, which leads to elevated blood pressure in adult rats, results in decreased levels of docosahexaenoic acid (DHA) in neonatal rat brain. In light of the evidence of a relationship between dietary DHA and adult blood pressure, the purpose of this study was to ascertain whether prenatal dietary supplementation with DHA would prevent the development of hypertension associated with maternal protein restriction. Throughout gestation, female Wistar rats were fed isocaloric diets containing either 18% casein+10% corn oil (CON; control), 9% casein+10% corn oil (LP; low-protein) or 9% casein+8.5% corn oil+1.5% DHASCO (LP+0.6% DHA). DHA increased levels of DHA in neonatal forebrain but there were no effects of LP. At 10 weeks there were no dietary effects on blood pressure measured on four consecutive days using tail-cuff plethysmography. There were also no significant effects measured at 30 weeks, using femoral artery catheterisation, despite adequate power to detect a 10 mm Hg difference. Trends in corticosterone measurements suggested higher stress reactivity in the LP group. These results do not provide strong support for the prenatal low protein model of hypertension and a relation with dietary DHA.

Birthweights, maternal cardiovascular events, and Barker hypothesis

It is well established that the intrauterine environment has an important impact on the subsequent health of various animals. 1 Langley SC Jackson AA Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin Sci (Colch). 1994; 86: 217-222 Google Scholar However, whether intrauterine programming determines certain aspects of adult health in human beings remains controversial. 2 Paneth N Susser M Early origin of coronary heart disease (the “Barker hypothesis”). BMJ. 1995; 310: 411-412 Crossref PubMed Scopus (250) Google Scholar , 3 Susser M Levin B Ordeals for the fetal programming hypothesis. BMJ. 1999; 318: 885-886 Crossref PubMed Scopus (41) Google Scholar Several anthropometric variables present at birth or in early infancy have been associated with the development in adulthood of risk factors for cardiovascular disease—ie, hypertension or diabetes—or of coronary heart disease itself. 4 Barker DJP Mothers, babies and disease in later life. BMJ Publishing, London1994 Google Scholar The many reports on this topic have polarised clinicians and scientists into camps of believers and non-believers. This segregation has even extended into the publication of the reports in The Lancet or the BMJ. 5 Ben-Schlomo Y Davey Smith G “Place of publication” bias?. BMJ. 1994; 309: 274 Crossref PubMed Scopus (8) Google Scholar Birthweight, early environment, and genetics: a study of twins discordant for acute myocardial infarctionThe lack of an association between birth characteristics and AMI within twin pairs suggests that previously reported associations may be influenced by genetic and early environmental factors, or possibly, by unmeasured maternal factors that operate independently of birthweight. Full-Text PDF Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129 290 birthsComplications of pregnancy linked to low birthweight are associated with an increased risk of subsequent IHD in the mother. Common genetic risk factors might explain the link between birthweight and risk of IHD in both the individual and the mother. Full-Text PDF

Intra-uterine growth retardation results in increased cardiac arrhythmias and raised diastolic blood pressure in adult rats.

Epidemiological evidence in humans suggests that intrauterine growth retardation is associated with an increased risk of hypertension and coronary heart disease in later life. To begin to understand the mechanisms involved, we developed and exploited a rat model of intrauterine growth retardation to assess predisposition to arrhythmias and resting blood pressure levels at defined ages from 4 to 18 months. Isolated working heart experiments were carried out on rats that had been subjected to intrauterine growth retardation by prenatal protein deprivation and age-matched male Wistar controls to measure susceptibility to wall stress-induced arrhythmias. In addition, resting systolic and diastolic blood pressures were measured in conscious rats via an indwelling arterial catheter. Hearts from intrauterine growth retarded animals showed significantly more ventricular premature beats and more episodes of ventricular tachycardia at all ages examined (4, 9 and 18 months), and at 4 and 18 months, a reduction in coronary blood flow. Diastolic pressure was significantly raised by intrauterine growth retardation in both groups examined (4 and 9 months). Protein malnutrition during the intrauterine period results in profound intrauterine growth retardation that is associated with a raised diastolic blood pressure and an increased predisposition to cardiac arrhythmias in later life. These results are consistent with epidemiological observations made in human populations, and as similar pathophysiological changes may operate in both situations, intrauterine protein deprivation may be a useful model to help define some of the mechanisms involved.

Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets.

1. Possible associations between maternal nutrition in pregnancy and non-communicable diseases of adulthood were assessed using a rat model. Rats were habituated to diets containing a range of protein levels (18, 12, 9 and 6% by weight), over a 14 day period, before mating. The low protein diets were maintained throughout pregnancy. Lactating mothers and their offspring were transferred to a standard chow diet (20% protein). 2. Pregnant rats demonstrated a graded response to the diets, with those fed 9 and 6% protein tending to consume less energy and gain less weight than 18% protein fed controls. Litter size and newborn death rates were not significantly altered by the low protein diets. 3. Offspring of 12 and 9% protein fed dams were grossly normal, gaining weight at a similar rate to those born to 18% protein fed control rats. Offspring of the 6% protein fed dams were smaller than pups from all other groups, over a 21 week period. 4. At 9 weeks of age, systolic blood pressure was determined in the offspring. All offspring from the three low protein groups were found to have significantly elevated blood pressure (15-22 mmHg) relative to the control group. An inverse relationship between maternal protein intake and the systolic blood pressure of the offspring was observed. Blood pressure remained elevated in the offspring of the 9 and 6% protein fed dams until 21 weeks of age. The observed hypertension was associated with increased pulmonary angiotensin-converting enzyme activity in the low protein groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial baroreflex control of heart period is not related to blood pressure variability in conscious hypertensive and normotensive rats.

1. The short-term (within 30 min periods) and the long-term (among 30 min periods) variabilities, expressed as variation coefficients, of blood pressure (BP) and heart period (HP) were studied using a computer analysis of BP recordings in freely moving genetically hypertensive (LH), normotensive (LN) and low BP (LL) rats of Lyon strains at ages 5, 9, 21 and 40 weeks. The baroreflex control of HP was estimated with the slope of the linear relationship between systolic BP (SBP) and HP (SBP-HP slope) computed after phenylephrine and nitroglycerin injections. 2. Short-term variability of BP increased between 5 and 9 weeks of age and then remained stable. Hypertension was accompanied by an increase in both short- and long-term variabilities of diastolic BP in adult rats. 3. A sharp increase in SBP-HP slope was observed between 5 and 9 weeks of age in LN rats. SBP-HP slope of LH rats increased slightly up to 21 weeks but remained lower than that of normotensive controls. 4. The weak inverse correlation existing between SBP-HP slope and BP variability appeared to be mediated by the BP level. In addition, atropine which is known to abolish almost completely the SBP-HP slope, did not increase BP variability. It is concluded that SBP-HP slope is not linearly associated with BP variability in conscious rats.

Factors contributing to the maintenance of arterial blood pressure in adult rats treated neonatally with guanethidine.

Adult rats treated neonatally with guanethidine had normal arterial blood pressures, but these were more dependent on the renin-angiotensin system than in control animals. Antagonism of V1-receptors (with d(CH2)5DAVP) enhanced the depressor effects of captopril in guanethidine-treated animals, but blood pressure was unaffected by this manoeuvre in control animals. Although there is evidence that sympathetic efferent vasomotor function is abolished following the schedule of neonatal guanethidine treatment used, pentolinium had a hypotensive effect in the presence of d(CH2)5DAVP and captopril, indicating that the adrenal medulla could have been contributing to the maintenance of blood pressure. This is consistent with the finding of marked supersensitivity to exogenous adrenaline in guanethidine-treated rats.

The influence of neonatal treatment with capsaicin on the control of blood pressure in adult rats in water-replete and water-deprived states.

Arterial blood pressures and heart rates were measured in water-replete and in water-deprived (48 h) conscious, adult rats that had received capsaicin (50 mg kg-1) or its vehicle neonatally. Resting arterial blood pressures and heart rates in capsaicin-treated rats were not different from the controls in either the water-replete or the water-deprived state. Inhibition of the vascular actions of vasopressin (with 1-beta-mercapto,-beta, beta-cyclopentamethylenepropionic acid, 8-D-arginine vasopressin, (d(CH2)5DAVP] had no significant effect on blood pressures in the water-replete animals but caused a significant hypotension in water-deprived rats; the magnitude of the hypotension was the same irrespective of whether the animals had received capsaicin or its vehicle. During angiotensin converting enzyme inhibition (with captopril) and ganglion blockade (with pentolinium), the vasopressin-mediated blood pressure recovery was more gradual in the capsaicin-treated animals than in the controls, but after 60 min blood pressures were similar in all groups. Collectively the results indicate that although the full development of vasopressin-dependent mechanisms following acute hypotension takes longer when a large proportion of unmyelinated afferent fibres have been destroyed by neonatal treatment with capsaicin, 48 h of water deprivation results in a normal involvement of vasopressin-dependent mechanisms in the maintenance of blood pressure.

Effect of age on hypertensive stimuli and the development of hypertension in Brattleboro rats.

1. In rats with inherited diabetes insipidus, unilateral nephrectomy plus drinking of 0.6% NaCl solution (saline) did not influence blood pressure in adult rats. However, when these factors applied before puberty, they produced hypertension. 2. We therefore analysed whether saline administration before puberty or unilateral nephrectomy before puberty was more important for this hypertensive response. 3. Saline drinking was found to be necessary for the response because hypertension was elicited by unilateral nephrectomy in adult rats only if saline consumption began before puberty.