Hypertension in SHR rats: contribution of maternal environment

1987 ◽  
Vol 253 (4) ◽  
pp. H980-H984 ◽  
Author(s):  
M. A. Cierpial ◽  
R. McCarty
Keyword(s):  
Shr Rats ◽  
Maternal Environment ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Rearing Conditions ◽  
Blood Pressures ◽  
Wistar Kyoto ◽  
Male Subjects ◽  
Cross Fostering

The role of the maternal environment in the development of hypertension in spontaneously hypertensive (SHR) rats was evaluated using the technique of reciprocal cross fostering. Litters of SHR and Wistar-Kyoto (WKY) normotensive pups were either reared by their natural mothers, in fostered to mothers of the same strain, or cross fostered to mothers of the opposite strain shortly after birth. Litters were weaned at 21 days of age, at which time all pups were weighed. At 18-20 wk of age, resting mean arterial blood pressures (MAP) and heart rates were determined for male subjects from the six groups (2 strains X 3 rearing conditions) via an indwelling tail artery catheter. At weaning, SHR animals weighed less than WKY animals. SHRs fostered to WKY mothers were significantly heavier than control SHRs, and WKYs fostered to SHR mothers were significantly lighter than WKY controls at weaning. These body weight differences were also evident in adulthood. Cross fostering SHR pups to normotensive WKY mothers resulted in a dramatic reduction in resting MAP measured in adulthood. Conversely, cross fostering WKY pups to SHR mothers had no measurable effect on adult resting MAP. We propose that an interaction between characteristics of the SHR maternal environment and a genetic susceptibility in SHR pups is essential in triggering the full expression of the hypertensive phenotype in this animal model of human essential hypertension.

Maternal influences on sympathetic-adrenal medullary system in spontaneously hypertensive rats

1990 ◽  
Vol 258 (5) ◽  
pp. H1312-H1316
Author(s):  
M. A. Cierpial ◽  
M. Konarska ◽  
R. McCarty
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Acute Stress ◽  
Hypertensive Rats ◽  
Blood Pressure Lowering Effect ◽  
Maternal Environment ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Wistar Kyoto ◽  
Cross Fostering

The technique of reciprocal cross fostering was used to assess the influence of the maternal environment on the functioning of the sympathetic-adrenal medullary system in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive rats. Control, in-fostered, and cross-fostered rats were tested in adulthood to assess 1) the neural contribution to resting mean arterial blood pressure (MAP) and 2) sympathetic-adrenal medullary responses to acute footshock stress. Adult resting MAP was significantly lower in cross-fostered SHRs (139.6 mmHg) compared with control or in-fostered SHRs (162.1 and 159.3 mmHg). In addition, the decrease in MAP after sympathetic blockade (40.6 mmHg) was significantly less in cross-fostered SHRs compared with controls (50.1 mmHg). Sympathetic-adrenal medullary responses to foot-shock were greater in SHR than WKY rats; however, cross-fostered SHRs showed exaggerated responses compared with control and in-fostered SHRs. Altering the maternal environment did not produce any measurable effects on the neural contribution to resting MAP or sympathetic-adrenal medullary responsivity to acute stress in the WKY strain. These results indicate that the blood pressure-lowering effect of cross fostering in the SHR strain is caused in part by a dampening of the neural contribution to resting MAP; however, these animals retain their strain's characteristic adrenergic hyperreactivity to stressful stimulation.

Plasma parathyroid hormone during the development of spontaneous hypertension in rats

1987 ◽  
Vol 65 (12) ◽  
pp. 2386-2389 ◽  
Author(s):  
P. K. T. Pang ◽  
S. Harvey ◽  
P. A. Doris
Keyword(s):  
Parathyroid Hormone ◽  
Spontaneously Hypertensive Rats ◽  
Spontaneous Hypertension ◽  
Hypertensive Rats ◽  
Intact Pth ◽  
Spontaneously Hypertensive ◽  
Blood Pressures ◽  
Wistar Kyoto ◽  
Tail Cuff

Plasma parathyroid hormone levels (pPTH) have been measured by radioimmunoassay (RIA) in young spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto controls (WKY) aged from 6 to 16 weeks to assess the possible role of PTH during the development of hypertension. Three antisera were used in the RIAs. One antiserum was directed toward the inactive C-terminal fragment of PTH, another toward the bioactive N-terrninal fragment (PTH 1–34), and a third was obtained by immunization against intact PTH 1–84. Blood pressures were measured by tail-cuff plethysmography with prewarming. Blood ionized calcium and sodium concentrations (b[Ca2+] and b[Na+]) were determined by ion-selective electrolyte analysis. No significant differences were observed between pPTH in the SHR compared with WKY during the development of hypertension. Neither were significant differences in b[Ca2+] or b[Na+] present at any age. The expected progression of hypertension in SHRs was observed and blood pressure was significantly greater in SHR than in WKY at all times. The results suggest that differences in pPTH and b[Ca2+] in SHR reported in other studies may be secondary phenomena to the establishment of hypertension. Our data suggest that PTH is not involved in the pathogenetic processes occurring during the development of spontaneous hypertension in rats.

scholarly journals Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

2011 ◽  
Vol 301 (4) ◽  
pp. R958-R966 ◽  
Author(s):  
Marina T. Cavalleri ◽  
Katia Burgi ◽  
Josiane C. Cruz ◽  
Maria T. Jordão ◽  
Alexandre Ceroni ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Shr Rats ◽  
Baroreflex Control ◽  
Spontaneously Hypertensive ◽  
Beneficial Effects ◽  
Wistar Kyoto ◽  
Afferent Signaling ◽  
And Training ◽  
Hemodynamic Measurements

We showed previously that oxytocinergic (OTergic) projections from the hypothalamic paraventricular nucleus (PVN) to the dorsal brain stem mediate training-induced heart rate (HR) adjustments and that beneficial effects of training are blocked by sinoaortic denervation (SAD; Exp Physiol 94: 630–640; 1103–1113, 2009). We sought now to determine the combined effect of training and SAD on PVN OTergic neurons in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats underwent SAD or sham surgery and were trained (55% of maximal capacity) or kept sedentary for 3 mo. After hemodynamic measurements were taken at rest, rats were deeply anesthetized. Fresh brains were frozen and sliced to isolate the PVN; samples were processed for OT expression (real-time PCR) and fixed brains were processed for OT immunofluorescence. In sham rats, training improved treadmill performance and increased the gain of baroreflex control of HR. Training reduced resting HR (−8%) in both groups, with a fall in blood pressure (−10%) only in SHR rats. These changes were accompanied by marked increases in PVN OT mRNA expression (3.9- and 2.2-fold in WKY and SHR rats, respectively) and peptide density in PVN OTergic neurons (2.6-fold in both groups), with significant correlations between OT content and training-induced resting bradycardia. SAD abolished PVN OT mRNA expression and markedly reduced PVN OT density in WKY and SHR. Training had no effect on HR, PVN OT mRNA, or OT content following SAD. The chronic absence of inputs from baroreceptors and chemoreceptors uncovers the pivotal role of afferent signaling in driving both the plasticity and activity of PVN OTergic neurons, as well as the beneficial effects of training on cardiovascular control.

Hyperresponsivitiy of spontaneously hypertensive rat to indirect measurement of blood pressure

1978 ◽  
Vol 234 (6) ◽  
pp. H690-H695 ◽  
Author(s):  
C. C. Chiueh ◽  
I. J. Kopin
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Catecholamines ◽  
Indirect Measurement ◽  
Shr Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Arterial Blood ◽  
Chromatographic Procedure ◽  
Wistar Kyoto

A chronic, indwelling, tail arterial cannula was implated in conscious undisturbed rats for measurement of blood pressure and heart rate and for obtaining blood samples. As an index of sympathetic activity, plasma levels of catecholamines in arterial blood of conscious animals were assayed by a radioenzymatic, paper-chromatographic procedure. Blood pressures of unrestrained spontaneously hypertensive (SHR) rats in their home cages (161 +/- 3/141 +/- 4 mmHg) were not different from those of pentobarbitol-anesthetized, hypertensive animals but were about 25 mmHg lower than awake animals during the restraint required for the tail-cuff procedure. Basal levels of plasma catecholamines in awake, undisturbed or in pentobarbital-anesthetized animals were similar in age-matched SHR and normotensive Wistar-Kyoto (WKY) rats. SHR rats were shown to have greater increase in plasma catecholamines than WKY rats during forced immobilization or restraint for indirect measurement of blood pressure.

Vascular reactivity, tissue levels, and binding sites for endothelin: a comparison in the spontaneously hypertensive and Wistar–Kyoto rats

1991 ◽  
Vol 69 (3) ◽  
pp. 406-413 ◽  
Author(s):  
Gordon T. Bolger ◽  
Francine Liard ◽  
Annette Jodoin ◽  
Jorge Jaramillo
Keyword(s):  
Blood Pressure ◽  
Binding Sites ◽  
Vascular Reactivity ◽  
Spontaneously Hypertensive Rat ◽  
Peripheral Resistance ◽  
Shr Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Arterial Blood ◽  
Wistar Kyoto

The role of endothelin (ET-1) in mediating the development of blood pressure was investigated in the spontaneously hypertensive (SHR) rat using the Wistar–Kyoto (WKY) rat as the normotensive control. The following were characterized in both rat strains: age-dependent changes in mean arterial blood pressure (MAP), tissue (blood, lung, heart, and kidney) levels of immunoreactive ET-1 like related peptides (ET-1RP), aortic ring responses to ET-1, and specific high-affinity tissue (lung, atrium, ventricle, aorta, and kidney) binding sites for 125I-labelled ET-1. Commencing at age 10 weeks through to 12 weeks, SHR rats but not WKY rats developed a significant increase in MAP (from 152 ± 7 to 189 ± 3 mmHg) (1 mmHg = 133.32 Pa). However, in both WKY and SHR rats immunoreactive levels of ET-1RP increased (100 and 80%, respectively) throughout the same measurement period. The potency of ET-1 to contract aortic rings from SHR rats was slightly but not significantly greater than that for aortic rings from WKY rats, although aortic rings from SHR rats contracted in the presence of 0.5 nM ET-1, while those from WKY rats did not. The levels of immunoreactive ET-1RP were significantly reduced (32%) in the kidney and unchanged in the heart and lung of SHR rats compared with WKY rats. Specific 125I-labelled ET-1 binding sites displayed an increase and a significant decrease (24%) of density in the atrium and ventricle, respectively, a significant increase (31%) of affinity in the lung, and were unchanged in the kidney and aorta of SHR rats compared with WKY rats following the development of hypertension. The lack of a correlation between circulating levels of immunoreactive ET-1RP and the development of hypertension coupled with a lack of significant differences in vascular reactivity suggest that ET-1 is not the sole mediator of hypertension in this animal model. However, the tissue-specific changes in immunoreactive ET-1RP and 125I-labelled ET-1 binding sites suggest that ET-1 may be a partial mediator of hypertension and is subject to compensatory changes in response to the increased total peripheral resistance in SHR rats.Key words: endothelin, hypertension, spontaneously hypertensive rat.

Increased Pressor Responsiveness to Enkephalin in Spontaneously Hypertensive Rats: The Role of Vasopressin

1980 ◽  
Vol 59 (s6) ◽  
pp. 235s-237s ◽  
Author(s):  
R. W. Rockhold ◽  
J. T. Crofton ◽  
L. Share
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pressor Response ◽  
Cardiovascular Effects ◽  
Hypertensive Rats ◽  
Methionine Enkephalin ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.

Role of adenosine in noradrenergic neurotransmission in spontaneously hypertensive rats

1987 ◽  
Vol 253 (4) ◽  
pp. H909-H918 ◽  
Author(s):  
E. K. Jackson
Keyword(s):  
Plasma Levels ◽  
Spontaneously Hypertensive Rat ◽  
Base Line ◽  
Inhibitory Effects ◽  
Spontaneously Hypertensive ◽  
Vascular Responses ◽  
Rat Mesentery ◽  
Wistar Kyoto

The purpose of this study was to compare the in vivo role of adenosine as a modulator of noradrenergic neurotransmission in the spontaneously hypertensive rat (SHR) and Wistar-Kyoto control rat (WKY). In the in situ blood-perfused rat mesentery, vascular responses to periarterial (sympathetic) nerve stimulation (PNS) and to exogenous norepinephrine (NE) were enhanced in SHR compared with WKY. In both SHR and WKY, vascular responses to PNS were more sensitive to inhibition by adenosine than were responses to NE. At matched base-line vascular responses, compared with WKY, SHR were less sensitive to the inhibitory effects of adenosine on vascular responses to PNS, but SHR and WKY were equally sensitive with respect to adenosine-induced inhibition of responses to NE. Antagonism of adenosine receptors with 1,3-dipropyl-8-p-sulfophenylxanthine shifted the dose-response curve to exogenous adenosine sixfold to the right yet did not influence vascular responses to PNS or NE in either SHR or WKY. Furthermore, PNS did not alter either arterial or mesenteric venous plasma levels of adenosine in SHR or WKY, and plasma levels of adenosine in both strains were always lower than the calculated threshold level required to attenuate neurotransmission. It is concluded that in vivo 1) exogenous adenosine interferes with noradrenergic neurotransmission in both SHR and WKY; 2) SHR are less sensitive to the inhibitory effects of exogenous adenosine on noradrenergic neurotransmission than are WKY; 3) endogenous adenosine does not play a role in modulating neurotransmission in either strain under the conditions of this study; and 4) enhanced noradrenergic neurotransmission in the SHR is not due to defective modulation of neurotransmission by adenosine.

Pharmacological and genetic evidence that cathepsin B is not the physiological activator of rodent prorenin

2010 ◽  
Vol 391 (12) ◽  
Author(s):  
M. David Percival ◽  
Sylvie Toulmond ◽  
Nathalie Coulombe ◽  
Wanda Cromlish ◽  
Sylvie Desmarais ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Cathepsin B ◽  
Plasma Renin ◽  
Renin Activity ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Arterial Blood ◽  
Gene Compensation

Abstract Renin is the first enzyme in the renin-angiotensin-aldosterone system which is the principal regulator of blood pressure and hydroelectrolyte balance. Previous studies suggest that cathepsin B is the activator of the prorenin zymogen. Here, we show no difference in plasma renin activity, or mean arterial blood pressure between wild-type and cathepsin B knockout mice. To account for potential gene compensation, a potent, selective, reversible cathepsin B inhibitor was developed to determine the role of cathepsin B on prorenin processing in rats. Pharmacological inhibition of cathepsin B in spontaneously hypertensive and double transgenic rats did not result in a reduction in renal mature renin protein levels or plasma renin activity. We conclude that cathepsin B does not play a significant role in this process in rodents.

Further analysis of cell membrane changes in genetic hypertension in rats by diphenylhexatriene fluorescence polarization

1984 ◽  
Vol 66 (6) ◽  
pp. 717-723 ◽  
Author(s):  
I. Aracon-Birlouez ◽  
T. Montenay-Carestier ◽  
M. A. Devynck
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Erythrocyte Membranes ◽  
Shr Rats ◽  
Erythrocyte Ghosts ◽  
Hypertensive Rats ◽  
Salt Loading ◽  
Spontaneously Hypertensive ◽  
Platelet Membranes ◽  
Wistar Kyoto ◽  
Membrane Changes

1. Fluorescence Dolarization of dbhenvlhexa-triene embedded in membranes was used as an index of ‘microviscosity’ in platelets and ervthro—cyte ghosts of spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR), Wistar-Kyoto strain (WKY) and of the hypertension-prone and -resistant Sabra strains (SBH and SBN), and the original Sabra strain (SB). 2. Microviscosity was increased both in erythrocyte ghosts and platelet membranes of male but not female SHR rats compared with WKY rats and in hypertension-prone Sabra rats compared with the original Sabra rats. 3. Acute and chronic salt loading increased the microviscosity of platelet membranes in all strains of rats but had no effect on the erythrocyte membranes. 4. Microviscosities of vesicles made of lipids extracted from SHR and WKY erythrocyte ghosts were similar. This supports the hypothesis that membrane proteins play a major role in the differences in microviscosity observed in SHR rats.

scholarly journals Long‐Term Dipeptidyl Peptidase 4 Inhibition Worsens Hypertension and Renal and Cardiac Abnormalities in Obese Spontaneously Hypertensive Heart Failure Rats

2021 ◽  
Author(s):  
Edwin K. Jackson ◽  
Zaichuan Mi ◽  
Delbert G. Gillespie ◽  
Dongmei Cheng ◽  
Stevan P. Tofovic
Keyword(s):  
Heart Failure ◽  
Collagen Iv ◽  
Spontaneously Hypertensive ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitor ◽  
Arterial Blood ◽  
Spontaneously Hypertensive Heart Failure ◽  
Blood Pressures ◽  
Renal Vascular

Background The long‐term effects of dipeptidyl peptidase 4 (DPP4) inhibitors on blood pressure and cardiovascular and renal health remain controversial. Herein, we investigated the extended (>182 days) effects of DPP4 inhibition in a model of spontaneous hypertension, heart failure, diabetes mellitus, obesity and hyperlipidemia. Methods and Results Adult obese spontaneously hypertensive heart failure rats (SHHF) were implanted with radio transmitters for measurement of arterial blood pressures. Two weeks later, SHHF were randomized to receive either a DPP4 inhibitor (sitagliptin, 80 mg/kg per day in drinking water) or placebo. At the end of the radiotelemetry measurements, renal and cardiac function and histology, as well as other relevant biochemical parameters, were assessed. For the first 25 days, mean arterial blood pressures were similar in sitagliptin‐treated versus control SHHF; afterwards, mean arterial blood pressures increased more in sitagliptin‐treated SHHF ( P <0.000001). The time‐averaged mean arterial blood pressures from day 26 through 182 were 7.2 mm Hg higher in sitagliptin‐treated SHHF. Similar changes were observed for systolic (8.6 mm Hg) and diastolic (6.1 mm Hg) blood pressures, and sitagliptin augmented hypertension throughout the light‐dark cycle. Long‐term sitagliptin treatment also increased kidney weights, renal vascular resistances, the excretion of kidney injury molecule‐1 (indicates injury to proximal tubules), renal interstitial fibrosis, glomerulosclerosis, renal vascular hypertrophy, left ventricular dysfunction, right ventricular degeneration, and the ratios of collagen IV/collagen III and collagen IV/laminin in the right ventricle. Conclusions These findings indicate that, in some genetic backgrounds, long‐term DPP4 inhibitor treatment is harmful and identify an animal model to study mechanisms of, and test ways to prevent, DPP4 inhibitor–induced pathological conditions.

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