Pathogenesis of abnormal acid–base balance in the young spontaneously hypertensive rat

1. We have previously reported reduced blood pH and plasma bicarbonate in young Okamoto–Aoki spontaneously hypertensive rats (SHR) compared with normotensive Wistar–Kyoto rats (WKY). Acid loading with 1.5% (w/v) NH4Cl as the sole drinking fluid produced identical falls in blood pH, the difference remaining significant. 2. The ability of SHR to excrete acid and alkaline loads was compared with that of WKY under metabolic cage conditions. The effects of such manipulations on urinary sodium, potassium, calcium and phosphate excretion were also determined. 3. No difference was found in the ability to excrete an acid load or to reduce urine pH. Neither total urinary ammonium ion nor titratable acid differed significantly between the strains under either baseline or acid-loading conditions. 4. Baseline urinary bicarbonate excretion was not significantly different between strains but intraperitoneal administration of NaHCO3 at 2.0 mmol/kg body weight resulted in enhanced excretion in the SHR (SHR vs WKY: 625.2±71.5 vs 381.8±40.6 μmol 24h−1 kg−1 body weight, P < 0.01, mean±sem). 5. No difference in urinary sodium or potassium excretion was observed between SHR and WKY, but basal calcium and phosphate excretion were reduced in SHR (P < 0.05). 6. Increased urinary bicarbonate excretion in the presence of significantly reduced plasma bicarbonate suggests reduced tubular reabsorption of bicarbonate, which may contribute to the mild metabolic acidosis in young SHR.

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Disturbance of acid–base balance in the young spontaneously hypertensive rat

Clinical Science ◽

10.1042/cs0730211 ◽

1987 ◽

Vol 73 (2) ◽

pp. 211-215 ◽

Cited By ~ 30

Author(s):

P. A. Lucas ◽

B. Lacour ◽

D. A. McCarron ◽

T. Drüeke

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rat ◽

Ionized Calcium ◽

Acid Base Balance ◽

Acid Base ◽

Spontaneously Hypertensive ◽

Plasma Bicarbonate ◽

Blood Ph ◽

Base Balance ◽

Wistar Kyoto

1. The acid–base status of young spontaneously hypertensive rats (SHR) was compared with that of Wistar–Kyoto rats (WKY) in the steady state, after acid loading and after blood pressure had been maintained at normal levels from weaning. Whole blood ionized calcium was measured simultaneously. 2. In the prehypertensive stage (4 weeks of age), plasma bicarbonate was significantly lower in SHR than in WKY, while blood pH did not differ significantly. 3. After 6 weeks of age, blood pH and plasma bicarbonate were significantly lower in both anaesthetized and conscious SHR than in corresponding WKY. After 7 days administration of NH4Cl in the drinking fluid, both parameters decreased significantly in both strains and the difference in pH remained constant (0.05 pH unit, P < 0.01). 4. In none of the groups investigated did non-pH-adjusted ionized calcium differ significantly between the SHR and WKY. 5. Prevention of the development of hypertension in SHR by hydralazine treatment from weaning did not increase pH or bicarbonate compared with untreated SHR, indicating that the metabolic acidosis in the SHR was not a consequence of raised blood pressure. 6. Disturbance in acid–base balance may be involved in the pathogenesis of raised blood pressure in this animal model of genetic hypertension.

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Voiding behavior in awake unrestrained untethered spontaneously hypertensive and Wistar control rats

AJP Renal Physiology ◽

10.1152/ajprenal.00564.2020 ◽

2021 ◽

Author(s):

Christopher L Langdale ◽

Danielle J Degoski ◽

Philip H Milliken ◽

Warren M. Grill

Keyword(s):

Body Weight ◽

Water Consumption ◽

Genetic Model ◽

Spontaneously Hypertensive Rat ◽

Infusion Pump ◽

Bladder Capacity ◽

In Vivo Studies ◽

Spontaneously Hypertensive ◽

Voided Volume

The spontaneously hypertensive rat (SHR), a genetic model of high blood pressure, has also been studied as a potential model of overactive bladder (OAB). In vivo studies confirmed the presence of surrogate markers of OAB, including detrusor overactivity (DO), increased urinary frequency, decreased bladder capacity and voided volume, and afferent hypersensitivity to bladder irritation. However, these observations were during awake cystometry (CMG) using implanted bladder catheters tethered to an infusion pump and artificially filled. We conducted studies in awake unrestrained untethered age-matched female SHR and Wistar rats to quantify naïve consumption and voiding behavior and the effect of capsaicin desensitization on consumption and voiding behavior. Food and water consumption, body weight, voiding frequency (VF), and voided volume (VV) were recorded. Rats were placed in metabolism cages for 24 h, up to twice a week, from 17 to 37 weeks of age. In SHRs, body weight, food, and water consumption were decreased compared to Wistars. However, after normalizing for body weight, only water consumption was reduced. Wistars exhibited a diurnal pattern of voiding behavior. Compared to Wistars, SHRs showed smaller VV and lacked a diurnal voiding pattern such that VV was similar during both light cycles. No difference in VF was observed after normalizing for water consumption. We observed no change in SHR voiding behavior following capsaicin desensitization, which was in contrast to a prior awake in vivo cystometry study describing increased VV and micturition interval in SHRs, and suggests that C-fiber activity may not contribute to bladder hypersensitivity in SHRs.

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Analysis of BP response and Ca2+ metabolism using the saturation kinetics model

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.253.3.r501 ◽

1987 ◽

Vol 253 (3) ◽

pp. R501-R508

Author(s):

N. Karanja ◽

J. A. Metz ◽

L. P. Mercer ◽

D. A. McCarron

Keyword(s):

Blood Pressure ◽

Body Weight ◽

Bone Density ◽

Spontaneously Hypertensive Rat ◽

Kinetics Model ◽

Maximal Dose ◽

Spontaneously Hypertensive ◽

Rates Of Change ◽

Saturation Kinetics ◽

Serum Ionized Calcium

The provision of supplemental dietary calcium (dCa) lowers blood pressure (BP) in the spontaneously hypertensive rat (SHR). Whether calcium's antihypertensive effects can be expressed in the presence of potentially hypertensinogenic nutrients is not known. Furthermore, the amount of dCa required to attenuate hypertension in the SHR remains undetermined. Along with establishing the effects of dCa on BP under conditions of a high Na+ intake, we sought to define the lowest dose of dCa associated with the greatest attenuation in arterial pressure in the young SHR. Thirty-five 6-wk-old SHR were fed one of five diets containing either 0.1, 0.25, 0.5, 1.0, or 2.0% dCa. All diets contained 1.0% Na+. The rates of change (delta) in body weight, BP, and serum ionized calcium were determined between 6 and 20 wk of age. Bone density (BD) was measured only at 20 wk of age. The data were analyzed using the saturation kinetics model. Results indicate that the half-maximal dose (K50) of dCa needed to lower pressure is 0.67 +/- 0.18%, which is higher than the K50 for weight (0.23 +/- 0.18) and BD (0.36 +/- 0.22). It is concluded that supplemental dCa lowers BP despite a high Na+ intake. Furthermore, a dose of approximately 1.5 dCa is sufficient to attenuate the rate of hypertension in the young growing SHR.

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The Herbal Medicine Tian Ma Gou Teng Yen Alters the Development of High Blood Pressure in the Spontaneously Hypertensive Rat

The American Journal of Chinese Medicine ◽

10.1142/s0192415x89000309 ◽

1989 ◽

Vol 17 (03n04) ◽

pp. 211-219 ◽

Cited By ~ 6

Author(s):

Ting-Xin Zhang ◽

Yu-Fen Wang ◽

John Ciriello

Keyword(s):

Body Weight ◽

Spontaneously Hypertensive Rat ◽

Urine Volume ◽

Herbal Therapy ◽

General Development ◽

Spontaneously Hypertensive ◽

Hypertensive Rat ◽

Food And Water Intake ◽

Vasomotor Activity ◽

Herbal Prescription

In this study. the effect of the herbal prescription Tian Ma Gou Teng Yen (TGY), which is traditionally used to treat certain diseases associated with elevated arterial pressure (AP), on the general development of hypertension was investigated in the spontaneously hypertensive rat (SHR). An aqueous extract of TGY was given orally (0.5 ml/100g body weight) to 5 week old SHR twice a day for six consecutive days followed by one day without herbal therapy. The herbal prescription was administered until the SHR were 16 weeks of age. Admininstration of TGY significantly altered the development and prevented hypertension in SHR. On the other hand, heart rat, body weight, food and water intake, and urine volume and electrolytes were not altered. These data suggest that the effect of TGY on AP was through an action of TGY on sympathetic vasomotor activity.

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Consequences of weight cycling in obese spontaneously hypertensive rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1996.270.4.r864 ◽

1996 ◽

Vol 270 (4) ◽

pp. R864-R872 ◽

Cited By ~ 3

Author(s):

P. Ernsberger ◽

R. J. Koletsky ◽

J. S. Baskin ◽

L. A. Collins

Keyword(s):

Body Weight ◽

Spontaneously Hypertensive Rat ◽

Metabolic Efficiency ◽

Rapid Weight Loss ◽

Weight Cycling ◽

Very Low Calorie Diet ◽

Final Body Weight ◽

Spontaneously Hypertensive ◽

Calorie Diet ◽

Ad Libitum

We mimicked human weight cycling in the obese spontaneously hypertensive rat (SHROB) model of genetic obesity. A 12-day very low calorie diet (VLCD; 16.7% of baseline calories) was alternated with 4-6 wk of ad libitum chow refeeding for three cycles. Control SHROB ate chow ad libitum. VLCD induced rapid weight loss, but during refeeding all the lost weight was regained. Final body weight was higher in cycled rats than in ad libitum controls (149 +/- 5 vs. 117 +/- 7% of initial baseline). Less weight was lost as a percent of starting body weight during each successive VLCD, which could not be explained by aging. At death, retroperitoneal fat pads were heavier in cycled SHROB than in ad libitum controls (62 +/- 3 vs. 44 +/- 4 g). During the first 2 days after each VLCD, cycled rats overate significantly relative to ad libitum controls (88 +/- 2 vs. 78 +/- 3 kcal/day), but cumulative food intake throughout the duration of the experiment did not differ (11.4 +/- 0.6 vs. 11.7 +/- 0.1 Mcal). Compared with ad libitum-fed rats, food efficiency (g body wt gain/kcal) was increased during each refeeding period. Weight cycling elevated blood pressure above the initial baseline throughout refeeding. Refeeding hypertension was abolished by ganglionic blockade with chlorisondamine. Thus weight cycling in SHROB exacerbates obesity, metabolic efficiency, abdominal fat accumulation, sympathetic activity, and hypertension.

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